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    as cause of neonatal sepsis: case report and literature review. Sharma Deepak,Khan Jafar,Agarwal Sunil The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians is a rare cause of neonatal sepsis and can present with life threating complications, thus leading to increase in neonatal mortality and morbidity. The clinical features of neonatal infection are not different to neonatal sepsis caused by other gram-negative organism in this age group. The mode of transmission of neonatal is still not known and has been postulated to be both vertical and horizontal. The diagnosis of is made by growth of the organism in blood culture as Serum Widal test is not helpful in diagnosis. The management includes supportive care and intravenous antibiotics. We report two neonates who were admitted in our neonatal intensive care unit for neonatal sepsis and were diagnosed of having sepsis. 10.1080/14767058.2019.1614555
    Presepsin values as markers of severity of sepsis. Aliu-Bejta Ajete,Atelj Anita,Kurshumliu Mentor,Dreshaj Shemsedin,Baršić Bruno International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases OBJECTIVES:Biomarkers are widely used for rapid diagnosis of sepsis. This study evaluated the diagnostic accuracy of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) in differentiating sepsis severity as well as their association with Sepsis-related Organ Failure Assessment (SOFA) score. METHODS:One hundred septic patients from two university clinical centers were enrolled in the study during two time periods. New Sepsis-3 definitions were used for sepsis stratification. Biomarkers and SOFA score were evaluated four times during the illness. A sandwich ELISA kit was used for presepsin measurement. Generalized linear mixed effects model was used to test the changes in biomarkers concentrations and SOFA score values during the illness and to estimate the differences between severity groups. Multivariate analysis was used to test the association of biomarkers with SOFA score. RESULTS:Presepsin concentrations were significantly higher on admission in patients with septic shock (n = 34) compared to patients with sepsis (n = 66), mean ± SD: 128.5 ± 47.6 ng/mL vs. 88.6 ± 65.6 ng/mL, respectively (p < 0.001). The same was not observed for PCT and CRP; their concentrations did not differ significantly between severity groups. A strong correlation of presepsin with SOFA score was also found (p < 0.0001). CONCLUSIONS:Presepsin had a good diagnostic ability to differentiate septic shock from sepsis in the study groups. PCT and CRP failed in differentiating sepsis severity. 10.1016/j.ijid.2020.03.057
    Intravenous Immunoglobulin G Modulates the Expression of Sepsis-Induced Coagulopathy Factors and Increases Serum IgM Levels: A Prospective, Single-Center Intervention Study. Ando Yukihiro,Inoue Shigeaki,Kawashima Takahisa,Okashiro Masahiro,Kotani Joji,Nishiyama Takashi The Kobe journal of medical sciences Sepsis and sepsis-related multiple organ failure are major causes of mortality in intensive care unit (ICU) settings. This study aimed to determine the effect of intravenous immunoglobulin G (IVIgG) on different types of immunoglobulin and anti-coagulant factor types in sepsis patients. A single-center observational study of patients with sepsis, severe sepsis, or septic shock was conducted from August 2008 to March 2013. Patients were divided into the IVIgG (immunoglobulin G [IgG] <870 mg/dL; lower normal range) and non-IVIgG (IgG ≥870 mg/dL) groups. The IVIgG group received IVIgG for three days, and other standard medications. Serial measurements were taken of serum IgG, immunoglobulin A (IgA), immunoglobulin M (IgM), total plasminogen activator inhibitor 1 (tPAI-1), and protein C. Patients in the IVIgG treatment group had significantly higher serum IgM level on Days 4 and 7 than on Day 1, but no significant changes in IgM levels were observed in patients in the non-IVIgG group. Patients in the IVIgG treatment had lower tPAI-1 levels on Days 4 and 7 than on Day 1 and increased protein C levels on Day 7 compared to those on Days 1 and 4. There were no significant differences in tPAI-1 levels or protein C levels in the non-IVIgG group, although a similar trend was observed. IVIgG administration increased patients' serum IgM and protein C levels and decreased their serum tPAI-1 levels. IVIgG has potential application for preventing sepsis-induced coagulopathy and disseminated intravascular coagulation.
    Epidemiology of sepsis and septic shock. Chiu Catherine,Legrand Matthieu Current opinion in anaesthesiology PURPOSE OF REVIEW:The epidemiology of sepsis and septic shock has been challenging to study for multiple reasons. These include changing diagnostic definitions, as well a high concentration of sepsis-related studies published from high-income countries (HICs), despite a large global burden. This section attempts to address the incidence of sepsis throughout the years and worldwide. RECENT FINDINGS:The incidence of sepsis and septic shock has continued to increase since the first consensus definitions (Sepsis-1) were established in 1991, and the latest definitions (Sepsis-3) provide a better reflection of mortality risk for a diagnosis of sepsis. Several studies argue that the incidence of sepsis is overreported in HICs, based on billing and coding practices, and may lead to overutilization of resources. However, recent estimates of the true global burden of sepsis, including low-income countries, are likely much higher than reported, with calls for better allocation of resources. SUMMARY:The true epidemiology of sepsis worldwide continues to be a highly debated subject, and more research is needed among low-income countries and high-risk subpopulations. 10.1097/ACO.0000000000000958
    The role of platelet to mean platelet volume ratio in the identification of adult-onset still's disease from sepsis. Ge Suohua,Ma Yongbin,Xie Mengxiao,Qiao Tengfei,Zhou Jun Clinics (Sao Paulo, Brazil) OBJECTIVES:Inflammatory factors exert a significant role in the development of adult-onset Still's disease (AOSD) and sepsis. Although platelet counts and platelet parameters have long served as indicators for inflammatory diseases, their role in the differential diagnosis between adult-onset stilĺs disease and sepsis remains unclear. We designed this retrospective study to explore whether the platelet to mean platelet volume (MPV) ratio (PMR) can help to distinguish AOSD from sepsis. METHODS:A total of 110 AOSD patients and 84 sepsis patients were enrolled in the study. Seventy-three AOSD patients and 56 sepsis patients between January 2010 and June 2017 were enrolled in the test cohort to analyze PMR values, which was then validated in the validation cohort (37 AOSD patients and 28 sepsis patients between June 2017 and December 2019). RESULTS:The values of PMR were significantly higher in AOSD patients than in sepsis patients (test cohort, validation cohort, and entire cohort), In the test cohort, logistic regression analysis showed that PMR was an independent risk factor of AOSD (odds ratios [OR]: 9.22, 95% confidence interval [CI] 2.15-39.46, p=0.003). Further receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve was 0.735 (95% CI 0.631-0.839, p<0.001) for PMR alone and 0.925 (95% CI 0.869-0.980, p<0.001) for the combination of PMR and serum ferritin. Consistently, the validation cohort exhibited analogous results. CONCLUSIONS:PMR could be used as a single indicator or a complementary indicator to distinguish AOSD from sepsis. 10.6061/clinics/2021/e2307
    High-Density Lipoprotein, Mean Platelet Volume, and Uric Acid as Biomarkers for Outcomes in Patients With Sepsis: An Observational Study. Montero-Chacón Luis Bolívar,Padilla-Cuadra Juan Ignacio,Chiou Sy Han,Torrealba-Acosta Gabriel Journal of intensive care medicine BACKGROUND:We conducted an observational study evaluating the association between uric acid, mean platelet volume (MPV), and high-density lipoprotein (HDL) with complications and outcomes of patients with sepsis in a critical care setting. METHODS:We followed patients with a diagnosis of severe sepsis and septic shock for a maximum of 28 days. Main outcomes assessed included length of stay (LOS), the need for renal replacement therapy (RRT), assisted mechanical ventilation (AMV), and vasopressor support as well as in-unit mortality. RESULTS:The overall average age of the 37 patients enrolled was 48.1 (19.8) years; among them, 37.8% were male. Abdominal related (43.2%) and pulmonary (29.7%) were the main sites of infection. The overall Acute Physiology and Chronic Health Evaluation 2 (APACHE-2) median score was 19 (9-24). Acute kidney injury (AKI) was observed in 46.9% of the sample. In all, 54.1% required vasopressor support, 54.1% AMV, and 35.1% RRT. Patients with bacteremia were significantly more likely to require vasopressor support and those with urinary tract infections were significantly younger. We found increasing ΔMPV levels, higher APACHE-2 scores, lower HDL values, and a reduced age to be associated with a longer LOS. Higher scores on the APACHE-2 scale and lower levels of HDL significantly associated with higher odds for developing AKI. The need for vasopressor support was significantly associated with higher values of 72-hour MPV and with higher levels of baseline uric acid and lower values of initial HCO. Initial and 72-hour levels of MPV and higher scores in the APACHE-2 were all significantly correlated with the need for AMV. An increased probability of dying during follow-up was significantly correlated with increasing age. CONCLUSION:We were able to establish significant associations between our candidate biomarkers and relevant outcomes for patients with sepsis. Our results support the use of these low-cost biomarkers in the assessment of prognosis of patients with sepsis. 10.1177/0885066618772825
    Performance of prognostic markers in pediatric sepsis. Tonial Cristian Tedesco,Costa Caroline Abud Drumond,Andrades Gabriela Rupp Hanzen,Crestani Francielly,Bruno Francisco,Piva Jefferson Pedro,Garcia Pedro Celiny Ramos Jornal de pediatria OBJECTIVE:To evaluate the prognostic performance of the Pediatric Index of Mortality 2 (PIM2), ferritin, lactate, C-reactive protein (CRP), and leukocytes, alone and in combination, in pediatric patients with sepsis admitted to the pediatric intensive care unit (PICU). METHODS:A retrospective study was conducted in a PICU in Brazil. All patients aged 6 months to 18 years admitted with a diagnosis of sepsis were eligible for inclusion. Those with ferritin and C-reactive protein measured within 48h and lactate and leukocytes within 24h of admission were included in the prognostic performance analysis. RESULTS:Of 350 eligible patients with sepsis, 294 had undergone all measurements required for analysis and were included in the study. PIM2, ferritin, lactate, and CRP had good discriminatory power for mortality, with PIM2 and ferritin being superior to CRP. The cutoff values for PIM2 (> 14%), ferritin (> 135ng/mL), lactate (> 1.7mmol/L), and CRP (> 6.7mg/mL) were associated with mortality. The combination of ferritin, lactate, and CRP had a positive predictive value of 43% for mortality, similar to that of PIM2 alone (38.6%). The combined use of the three biomarkers plus PIM2 increased the positive predictive value to 76% and accuracy to 0.945. CONCLUSIONS:PIM2, ferritin, lactate, and CRP alone showed good prognostic performance for mortality in pediatric patients older than 6 months with sepsis. When combined, they were able to predict death in three-fourths of the patients with sepsis. Total leukocyte count was not useful as a prognostic marker. 10.1016/j.jped.2020.07.008
    Predicting Outcome in Neonates with Possible Clinical Sepsis by Estimating an Early Score for Neonatal Acute Physiology-II (SNAP-II). Pal Somalika,Jain Ashish,Garg Madhu,Sekhar Jerin C Journal of tropical pediatrics OBJECTIVES:To determine role of Score for Neonatal Acute Physiology-II (SNAP-II) and its individual parameters assessed within 12 h of suspicion of neonatal sepsis in predicting outcomes; study its distribution across gestational ages and determine its relation with survival duration among expired neonates. METHODS:This prospective observational study conducted in a newborn unit of a tertiary care teaching hospital over 1 year included intramural neonates with birth weight ≥1000 g and gestation ≥28 weeks suspected with sepsis and assigned SNAP-II score within 12 h of suspicion. On day 14 of enrollment, they were categorized into three outcome groups: death (D), survival with organ dysfunction (SOD) and survival without organ dysfunction (SWOD). RESULTS:One hundred and ten neonates were enrolled and 100 analyzed. Mean SNAP-II score was 22 ± 22 (median: 13; interquartile range: 5-32.5). Seventy-six percent, 16% and 8% neonates belonged to SWOD, D and SOD groups, respectively. SNAP-II score and its individual parameters varied significantly among all outcome groups (p < 0.001). SNAP-II cutoffs of 44/115, 44/115, 38/115 and 33/115 were found to be highly predictive of D, D vs. SOD, D/SOD vs. SWOD and SWOD vs. SOD, respectively (sensitivity: 87.5-99%; specificity: 75-99%). The score was unaffected by gestational age (p = 0.80). Neonates with culture positive sepsis/meningitis had higher SNAP-II scores (p = 0.001). CONCLUSIONS:SNAP-II and its individual parameters found to have high sensitivity and specificity in predicting outcomes in possible neonatal sepsis and may have a role in predicting severity of disease progression and rapidity of deterioration among non-survivors, pending validation in larger studies. 10.1093/tropej/fmz076
    Use of Intravenous Immunoglobulins in Sepsis Therapy-A Clinical View. Jarczak Dominik,Kluge Stefan,Nierhaus Axel International journal of molecular sciences Sepsis is a life-threatening organ dysfunction, defined by a dysregulated host immune response to infection. During sepsis, the finely tuned system of immunity, inflammation and anti-inflammation is disturbed in a variety of ways. Both pro-inflammatory and anti-inflammatory pathways are upregulated, activation of the coagulation cascade and complement and sepsis-induced lymphopenia occur. Due to the manifold interactions in this network, the use of IgM-enriched intravenous immunoglobulins seems to be a promising therapeutic approach. Unfortunately, there is still a lack of evidence-based data to answer the important questions of appropriate patient populations, optimal timing and dosage of intravenous immunoglobulins. With this review, we aim to provide an overview of the role of immunoglobulins, with emphasis on IgM-enriched formulations, in the therapy of adult patients with sepsis and septic shock. 10.3390/ijms21155543
    Admission platelet count and indices as predictors of outcome in children with severe Sepsis: a prospective hospital-based study. Sayed Samira Z,Mahmoud Mohamed M,Moness Hend M,Mousa Suzan O BMC pediatrics BACKGROUND:Sepsis is still one of the main causes of infants and children mortality especially in developing, economically challenged countries with limited resources. Our objective in this study was to determine, the prognostic value of platelet count, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) in critically ill infants and children with severe sepsis, as they are readily available biomarkers, that can guide clinicians during managing of severe sepsis. METHODS:Sixty children were included; they were diagnosed with severe sepsis according to the international pediatric sepsis consensus conference criteria. At admission to Pediatric intensive care unit, complete blood count with platelet count and parameters (MPV, PDW and PCT) and C-reactive protein (CRP) level were determined for all children. Also, assessment of the Pediatric Risk of Mortality (PRISM III) score was done to all. These children were followed up till discharge from hospital or death. Accordingly, they were grouped into: (1) Survivor group: included 41 children. (2) Non-survivor group: included 19 children. RESULTS:Platelet count and PCT were significantly lower (p < 0.001) and MPV was significantly higher in non-survivor than survivors (p = 0.004). MPV/PLT, MPV/PCT, PDW/PLT, PDW/PCT ratios were found to be significantly higher in the non-survivors than survivor (p < 0.001 in all). PCT with sensitivity = 94.74%, was the most sensitive platelet parameter for prediction of death, while MPV/PCT was the most sensitive ratio (sensitivity = 94.7%). CONCLUSION:Thrombocytopenia, platelet indices and their ratios, especially plateletcrit and MPV/PCT, are readily available, sensitive, prognostic markers, that can identify the severe sepsis patients with poorest outcome. 10.1186/s12887-020-02278-4
    Effect of zinc supplementation on relative expression of immune response genes in neonates with sepsis: A preliminary study. Banupriya Newton,Bhat Ballambattu Vishnu,Vickneshwaran Vinayagam,Sridhar Magadi Gopalakrishna The Indian journal of medical research Background & objectives:Zinc alters gene expression mainly by binding to a site on the transcription factor. Genome-wide expression studies have shown early repression of genes related to zinc and immunity in adult patients with sepsis. The present study was conducted to evaluate the role of zinc supplementation on relative expression of immune response genes in neonatal sepsis. Methods:In the present study, a sample of convenience of 22 neonates each was selected from the zinc supplemented and control groups using random numbers for expression of immune-related genes by zinc supplementation. These neonates with sepsis were earlier randomized into two groups: with and without zinc supplementation in addition to standard antibiotics and supportive care. Relative expression of immune response genes were analyzed for 22 neonates in each group using quantitative real-time PCR for calprotectin (S100A8/A9), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), toll-like receptor-4 (TLR-4), cluster of differentiation 14 (CD14) and lipopolysaccharide-binding protein (LBP) genes. Results:An increase in serum zinc levels was observed in zinc-supplemented group compared to controls. S100A8 gene showed downregulation by three-fold (P <0.001) and S100A9 gene showed upregulation by two-fold (P <0.05) in zinc group compared to controls. CD14 gene showed upregulation by one-fold in zinc-supplemented group compared to controls (P <0.05). No significant fold changes were observed with respect to TNF-α, IL-6, LBP and TLR-4 genes between the two groups. Interpretation & conclusions:The results of our preliminary study showed that the zinc supplementation might modulates the relative expression of immune-related genes involved in sepsis pathway among neonates. However, studies with larger sample size are needed to be done to provide a better picture on the outcome by gene expression in neonatal sepsis by zinc supplementation. 10.4103/ijmr.IJMR_557_18
    Serum total carbon dioxide as a prognostic factor for 28-day mortality in patients with sepsis. Kim Jin Hee,Jang Dong-Hyun,Jo You Hwan,Suh Gil Joon,Kwon Woon Yong,Lee Jae Hyuk,Shin Jonghwan,Park Inwon,Lee Che Uk,Lee Sang-Min The American journal of emergency medicine OBJECTIVE:Metabolic acidosis is commonly associated with the disease severity in patients with sepsis or septic shock. This study was performed to investigate the association between serum total carbon dioxide (TCO concentration and 28-day mortality in patients with sepsis. METHODS:This study was a multicenter retrospective cohort study of patients with sepsis or septic shock. The relationships between serum TCO and 28-day mortality, bicarbonate, pH, lactate, and anion gap were determined with cubic spline curves. The patients were divided into four groups according to their serum TCO concentration: Group I (TCO > 20 mmol/l), Group II (15 < TCO ≤ 20 mg/dl), Group III (10 < TCO ≤ 15 mmol/l), and Group IV (TCO ≤ 10 mmol/l). RESULTS:A total of 3168 patients were included in the analysis, and the overall mortality rate was 24.1%. Serum TCO concentrations below 20 mmol/l showed an almost linear correlation with mortality as well as with lactate, bicarbonate, and pH. The 28-day mortality rates of Group I, II, III, and IV were 18.3%, 23.6%, 32.6%, and 50.0%, respectively (p < .001). In Multivariable Cox proportional hazard regression analysis, the groups with lower serum TCO concentrations had a higher risk of 28-day mortality compared with Group I: Group II (Hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.11-1.64), Group III (HR, 1.74; 95% CI, 1.37-2.21), and Group IV (HR, 2.72; 95% CI, 2.03-3.64). CONCLUSIONS:Serum TCO concentrations of 20 mmol/l or less were associated with 28-day mortality in patients with sepsis. 10.1016/j.ajem.2020.04.006
    The development an artificial intelligence algorithm for early sepsis diagnosis in the intensive care unit. Yuan Kuo-Ching,Tsai Lung-Wen,Lee Ko-Han,Cheng Yi-Wei,Hsu Shou-Chieh,Lo Yu-Sheng,Chen Ray-Jade International journal of medical informatics BACKGROUND:Severe sepsis and septic shock are still the leading causes of death in Intensive Care Units (ICUs), and timely diagnosis is crucial for treatment outcomes. The progression of electronic medical records (EMR) offers the possibility of storing a large quantity of clinical data that can facilitate the development of artificial intelligence (AI) in medicine. However, several difficulties, such as poor structure and heterogenicity of the raw EMR data, are encountered when introducing AI with ICU data. Labor-intensive work, including manual data entry, personal medical records sorting, and laboratory results interpretation may hinder the progress of AI. In this article, we introduce the developing of an AI algorithm designed for sepsis diagnosis using pre-selected features; and compare the performance of the AI algorithm with SOFA score based diagnostic method. MATERIALS AND METHODS:This is a prospective open-label cohort study. A specialized EMR, named TED_ICU, was implemented for continuous data recording. One hundred six clinical features relevant to sepsis diagnosis were selected prospectively. A labeling work to allocate SEPSIS or NON_SEPSIS status for each ICU patient was performed by the in-charge intensivist according to SEPSIS-3 criteria, along with the automatic recording of selected features every day by TED_ICU. Afterward, we use de-identified data to develop the AI algorithm. Several machine learning methods were evaluated using 5-fold cross-validation, and XGBoost, a decision-tree based algorithm was adopted for our AI algorithm development due to best performance. RESULTS:The study was conducted between August 2018 and December 2018 for the first stage of analysis. We collected 1588 instances, including 444 SEPSIS and 1144 NON-SEPSIS, from 434 patients. The 434 patients included 259 (59.6%) male patients and 175 female patients. The mean age was 67.6-year-old, and the mean APACHE II score was 13.8. The SEPSIS cohort had a higher SOFA score and increased use of organ support treatment. The AI algorithm was developed with a shuffle method using 80% of the instances for training and 20% for testing. The established AI algorithm achieved the following: accuracy = 82% ± 1%; sensitivity = 65% ± 5%; specificity = 88% ± 2%; precision = 67% ± 3%; and F1 = 0.66 ± 0.02. The area under the receiver operating characteristic curve (AUROC) was approximately 0.89. The SOFA score was used on the same 1588 instances for sepsis diagnosis, and the result was inferior to our AI algorithm (AUROC = 0.596). CONCLUSION:Using real-time data, collected by EMR, from the ICU daily practice, our AI algorithm established with pre-selected features and XGBoost can provide a timely diagnosis of sepsis with an accuracy greater than 80%. AI algorithm also outperforms the SOFA score in sepsis diagnosis and exhibits practicality as clinicians can deploy appropriate treatment earlier. The early and precise response of this AI algorithm will result in cost reduction, outcome improvement, and benefit for healthcare systems, medical staff, and patients as well. 10.1016/j.ijmedinf.2020.104176
    [A clinical analysis of sepsis in very low birth weight infants]. Hu Xiao-Shan,Zhu Jin-Gai,Jiang Cheng-Yao,Chen Xiao-Hui,Yu Zhang-Bin,Han Shu-Ping Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the incidence and clinical features of sepsis in very low birth weight (VLBW) infants. METHODS:The clinical data were collected from VLBW infants, with a birth weight of < 1 500 g, who were admitted to the Department of Neonatology, Maternity Hospital Affiliated to Nanjing Medical University, from January 2019 to June 2020. The incidence of sepsis, distribution of pathogenic bacteria, and risk factors for sepsis were analyzed. RESULTS:A total of 369 infants were enrolled, and 138 infants had sepsis, among whom 84 had early-onset sepsis (EOS) and 54 had late-onset sepsis (LOS). (24%) and (21%) were the main pathogenic bacteria in infants with EOS, and (41%) and (29%) were the main pathogenic bacteria in infants with LOS. The incidence of EOS and LOS decreased with the increase of gestational age and birth weight ( < 0.05). The multivariate logistic regression analysis showed that a high birth weight was a protective factor against EOS (=0.996, 95%:0.993-0.998, < 0.05), while vaginal delivery (=2.781, 95%:1.190-6.500, < 0.05) was a risk factor for EOS, and long duration of parenteral nutrition was a risk factor for LOS (=1.129, 95%:1.067-1.194, < 0.05). CONCLUSIONS: is the most common pathogenic bacteria for EOS, and is the most common pathogenic bacterium for LOS in VLBW infants. A high birth weight may reduce the risk of EOS in VLBW infants, while vaginal delivery may increase the risk of EOS. Prolonged parenteral nutrition may increase the risk of LOS.
    Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Weiss Scott L,Peters Mark J,Alhazzani Waleed,Agus Michael S D,Flori Heidi R,Inwald David P,Nadel Simon,Schlapbach Luregn J,Tasker Robert C,Argent Andrew C,Brierley Joe,Carcillo Joseph,Carrol Enitan D,Carroll Christopher L,Cheifetz Ira M,Choong Karen,Cies Jeffry J,Cruz Andrea T,De Luca Daniele,Deep Akash,Faust Saul N,De Oliveira Claudio Flauzino,Hall Mark W,Ishimine Paul,Javouhey Etienne,Joosten Koen F M,Joshi Poonam,Karam Oliver,Kneyber Martin C J,Lemson Joris,MacLaren Graeme,Mehta Nilesh M,Møller Morten Hylander,Newth Christopher J L,Nguyen Trung C,Nishisaki Akira,Nunnally Mark E,Parker Margaret M,Paul Raina M,Randolph Adrienne G,Ranjit Suchitra,Romer Lewis H,Scott Halden F,Tume Lyvonne N,Verger Judy T,Williams Eric A,Wolf Joshua,Wong Hector R,Zimmerman Jerry J,Kissoon Niranjan,Tissieres Pierre Intensive care medicine OBJECTIVES:To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN:A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. CONCLUSIONS:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. 10.1007/s00134-019-05878-6
    Recent advances in developing biosensing based platforms for neonatal sepsis. Balayan Sapna,Chauhan Nidhi,Chandra Ramesh,Kuchhal Naresh K,Jain Utkarsh Biosensors & bioelectronics Neonatal sepsis is a bloodstream infection primarily caused by Escherichia coli (E. coli), Group B Streptococcus (GBS), Listeria monocytogenes, Haemophilus influenzae, S. aureus, Klebsiella spp. and non-typhoidal Salmonella bacteria. Neonatal Sepsis is referred as a critical response to the infection in the neonatal period that can lead to the failure of body organs and thereby causing damage to the tissues resulting in death of the neonates. Nearly 4 million deaths across the world are occurred due to neonatal sepsis infections. In order to prevent the bloodstream infections in the neonates, it is indispensable to diagnose the disease properly for appropriate treatment during the point of care. Numerous studies have been reported to identify major biomarkers associated with neonatal sepsis including Serum Amyloid A (SAA), C - reactive protein (CRP), Procalcitonin (PCT) and Lipopolysaccharide-binding protein (LBP). Distinct diagnostic platforms have also been developed detecting the presence of bloodstream infections including electrochemical, potentiometric, and impedimetric sensors. Recently, electrochemical biosensors with the integration of nanomaterials have emerged as a better platform for neonatal sepsis biomarkers detection. This review article summarizes the diverse screening platforms, evaluation parameters, and new advances based on implications of nanomaterials for the development of biosensors detecting neonatal sepsis infections. The review further elucidates the significance and future scope of distinctive platforms which are predominantly associated with detection of neonatal sepsis. 10.1016/j.bios.2020.112552
    A deep learning approach for sepsis monitoring via severity score estimation. Aşuroğlu Tunç,Oğul Hasan Computer methods and programs in biomedicine BACKGROUND AND OBJECTIVE:Sepsis occurs in response to an infection in the body and can progress to a fatal stage. Detection and monitoring of sepsis require multi-step analysis, which is time-consuming, costly and requires medically trained personnel. A metric called Sequential Organ Failure Assessment (SOFA) score is used to determine the severity of sepsis. This score depends heavily on laboratory measurements. In this study, we offer a computational solution for quantitatively monitoring sepsis symptoms and organ systems state without laboratory test. To this end, we propose to employ a regression-based analysis by using only seven vital signs that can be acquired from bedside in Intensive Care Unit (ICU) to predict the exact value of SOFA score of patients before sepsis occurrence. METHODS:A model called Deep SOFA-Sepsis Prediction Algorithm (DSPA) is introduced. In this model, we combined Convolutional Neural Networks (CNN) features with Random Forest (RF) algorithm to predict SOFA scores of sepsis patients. A subset of Medical Information Mart in Intensive Care (MIMIC) III dataset is used in experiments. 5154 samples are extracted as input. Ten-fold cross validation test are carried out for experiments. RESULTS:We demonstrated that our model has achieved a Correlation Coefficient (CC) of 0.863, a Mean Absolute Error (MAE) of 0.659, a Root Mean Square Error (RMSE) of 1.23 for predictions at sepsis onset. The accuracies of SOFA score predictions for 6 hours before sepsis onset were 0.842, 0.697, and 1.308, in terms of CC, MAE and RMSE, respectively. Our model outperformed traditional machine learning and deep learning models in regression analysis. We also evaluated our model's prediction performance for identifying sepsis patients in a binary classification setup. Our model achieved up to 0.982 AUC (Area Under Curve) for sepsis onset and 0.972 AUC for 6 hours before sepsis, which are higher than those reported by previous studies. CONCLUSIONS:By utilizing SOFA scores, our framework facilitates the prognose of sepsis and infected organ systems state. While previous studies focused only on predicting presence of sepsis, our model aims at providing a prognosis solution for sepsis. SOFA score estimation process in ICU depends on laboratory environment. This dependence causes delays in treating patients, which in turn may increase the risk of complications. By using easily accessible non-invasive vital signs that are routinely collected in ICU, our framework can eliminate this delay. We believe that the estimation of the SOFA score will also help health professionals to monitor organ states. 10.1016/j.cmpb.2020.105816
    Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Kyriazopoulou Evdoxia,Liaskou-Antoniou Lydia,Adamis George,Panagaki Antonia,Melachroinopoulos Nikolaos,Drakou Elina,Marousis Konstantinos,Chrysos Georgios,Spyrou Andronikos,Alexiou Nikolaos,Symbardi Styliani,Alexiou Zoi,Lagou Styliani,Kolonia Virginia,Gkavogianni Theologia,Kyprianou Miltiades,Anagnostopoulos Ioannis,Poulakou Garyfallia,Lada Malvina,Makina Anna,Roulia Efrosyni,Koupetori Marina,Apostolopoulos Vasileios,Petrou Dimitra,Nitsotolis Thomas,Antoniadou Anastasia,Giamarellos-Bourboulis Evangelos J American journal of respiratory and critical care medicine Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by or multidrug-resistant organisms, or any death attributed to baseline or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98;  = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89;  = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days ( < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm. In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304). 10.1164/rccm.202004-1201OC
    Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation. Wong Hector R,Reeder Ron W,Banks Russell,Berg Robert A,Meert Kathleen L,Hall Mark W,McQuillen Patrick S,Mourani Peter M,Chima Ranjit S,Sorenson Samuel,Varni James W,McGalliard Julie,Zimmerman Jerry J, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies OBJECTIVES:The Life After Pediatric Sepsis Evaluation investigation recently reported that one-third of children who survive sepsis experience significant health-related quality-of-life impairment compared with baseline at 1 year after hospitalization. Pediatric Sepsis Biomarker Risk Model is a multibiomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the Pediatric Sepsis Biomarker Risk Model biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term health-related quality-of-life morbidity among children with community-acquired septic shock. DESIGN:Secondary analysis. SETTING:Twelve academic PICUs. PATIENTS:A subset of Life After Pediatric Sepsis Evaluation subjects (n = 173) with available blood samples. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Three predefined outcomes from the Life After Pediatric Sepsis Evaluation investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or persistent, serious deterioration of health-related quality of life (> 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). Pediatric Sepsis Biomarker Risk Model had an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.59-0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, Pediatric Sepsis Biomarker Risk Model was not independently associated with increased odds of the composite outcome of mortality or deterioration of persistent, serious deterioration health-related quality of life greater than 25% below baseline. A new decision tree using the Pediatric Sepsis Biomarker Risk Model biomarkers had an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.80-0.95) for estimating the risk of persistent, serious deterioration health-related quality of life at 3 months among children who survived septic shock. CONCLUSIONS:Pediatric Sepsis Biomarker Risk Model had modest performance for estimating hospital mortality in an external cohort of children with community-acquired septic shock. The Pediatric Sepsis Biomarker Risk Model biomarkers appear to have utility for estimating the risk of persistent, serious deterioration of health-related quality of life up to 3 months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long-term health-related quality-of-life morbidity among children who survive septic shock. 10.1097/PCC.0000000000002572
    Exhaled end-tidal carbon dioxide as a predictor of lactate and pediatric sepsis. Cully Matthew,Treut Michael,Thompson Amy D,DePiero Andrew D The American journal of emergency medicine OBJECTIVE:The objective of this study was to investigate the relationship between exhaled end-tidal carbon dioxide (ETCO) and serum lactate via nasal capnography and to assess the ability of ETCO to predict disease severity in children with suspected sepsis in a pediatric emergency department. METHODS:This prospective study included patients (≥ 30 days to ≤21 years of age) who presented with suspected sepsis to a tertiary pediatric emergency department. Pearson correlation coefficient was generated to measure the linear relationship between ETCO and lactate. Receiver operating characteristic curves (ROC) were generated to assess the performance of ETCO to predict a lactate ≥2 mmol/L and severe disease. Severe disease was defined as severe sepsis and septic shock. RESULTS:From November 1, 2018 to March 31, 2020, 105 emergency department patients underwent evaluation for suspected sepsis. Sixty-nine patients met the inclusion criteria for the study. There was an inverse relationship between ETCO and lactate with a correlation coefficient of -0.34 (p = .005). Severe disease had lower ETCO (32 ± 6 mmHg, p < .001) and higher lactate (3.3 ± 1.7 mmol/L, p < .001). The area under the curve (AUC) for ETCO to predict severe disease was 0.75 (95% CI 0.63, 0.86). An ETCO cut off point of 30 mmHg correlated with a sensitivity of 93% and specificity of 32%. CONCLUSIONS:We observed a significant inverse relationship between ETCO2 and lactate in children presenting with suspected sepsis. A lower ETCO2 was predictive of severe disease. 10.1016/j.ajem.2020.07.075
    Cell-Surface Biomarkers, C-Reactive Protein and Haematological Parameters for Diagnosing Late Onset Sepsis in Pre-term Neonates. Rohil Aradhana,Dutta Sourabh,Varma Neelam,Sachdev Manupdesh Singh,Bansal Arun,Kumar Praveen Journal of tropical pediatrics OBJECTIVE:To compare the diagnostic accuracy of white blood cell-surface biomarkers (CD64, CD11b and HLA-DR), C-reactive protein (CRP) and hematological parameters to diagnose definite sepsis among pre-term neonates presenting with suspected late-onset neonatal sepsis (LONS). DESIGN:This was a prospective, single-gate, diagnostic study in a Level III neonatal unit. Fifty-three neonates (gestation, <34 weeks) with LONS (onset, >72  age), were enrolled. Cell-surface biomarkers, CRP and haematological parameters were assayed at 0 and 48 h after onset. The reference standard was definite sepsis, defined as a positive blood culture with a non-contaminant organism. The index tests (cell-surface biomarkers, CRP and haematological parameters) were compared between subjects with or without 'definite sepsis'. The area under the receiver operator characteristics curves (AUC) generated for each index test at 0 and 48 h was compared. SETTING:Level III neonatal unit in a tertiary care institute. RESULTS:Of 53 enrolled pre-term infants, 24 had definite sepsis. Among all the index tests evaluated, CRP at 48 h had the highest AUC [0.82 (95% confidence interval, 0.69, 0.92)]. The expression of CD11b and HLA-DR was significantly reduced among the septic neonates. Among the cell-surface biomarkers, the maximum AUC was recorded for HLA-DR at 48  [0.68 (95% CI, 0.54, 0.81)]. Comparisons between index tests were not statistically significant. CONCLUSION:C-reactive protein is superior to other sepsis screen biomarkers and white blood cell-surface biomarkers in diagnosing culture-positive LONS among pre-term infants. CD64, CD11b and HLA DR as diagnostic tests in this group have limited discriminatory value. LAY SUMMARY:The diagnosis of neonatal blood stream infections is a challenge. In response to bacterial blood stream infections, white blood cells are known to produce an excess of certain types of specialized proteins on their surface, including CD64, CD11b and HLA-DR. In this study we evaluated the concentration of these cell-surface proteins for diagnosing blood stream infections in pre-mature newborn babies, whose onset of infection was beyond 72 h of life. We compared these tests against standard tests that are currently in clinical use, such as C-reactive protein and blood white cell counts. All tests were performed at the time of initially suspecting the infection and 48 h later. The gold standard against which all these tests were evaluated was blood culture, in which the offending bacteria are grown in specialized laboratory media. Of 53 pre-mature babies with suspected infection, 24 had blood culture-proven infection. Among all tests, C-reactive protein at 48 h had the best ability to distinguish definite infection from no infection. The expression of CD11b and HLA-DR was significantly reduced among infected neonates. We conclude that C-reactive protein is superior to white blood cell-surface proteins and white cell count in diagnosing definite late-onset infections among pre-term infants. 10.1093/tropej/fmab016
    Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study. Agnello Luisa,Sasso Bruna Lo,Giglio Rosaria Vincenza,Bivona Giulia,Gambino Caterina Maria,Cortegiani Andrea,Ciaccio Anna Maria,Vidali Matteo,Ciaccio Marcello Annals of clinical biochemistry BACKGROUND:Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit. METHODS:In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital "P. Giaccone" of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3) and daily until the developing of sepsis (group 2) or the end of hospitalization (group 1). RESULTS:Monocyte distribution width was significantly higher in group 3 than group 1 and group 2 (30.9 [25.6-36.0] vs. 20.3 [18.3-23.6] and 21.4 [19.4-25.2]). Among patients belonging to group 2, monocyte distribution width values, measured at the day when sepsis was clinically diagnosed, were significantly higher than those found at admission: 29.4 (26.7-36.0) vs. 21.4 (19.4-25.2),  = 0.001. CONCLUSION:Monocyte distribution width could represent a reliable biomarker of sepsis in the intensive care unit. 10.1177/0004563220970447
    Comparison of the quick Sepsis-related Organ Failure Assessment and adult sepsis pathway in predicting adverse outcomes among adult patients in general wards: a retrospective observational cohort study. Li Ling,Rathnayake Kasun,Green Malcolm,Shetty Amith,Fullick Mary,Walter Scott,Middleton-Rennie Catriona,Meller Michael,Braithwaite Jeffrey,Lander Harvey,Westbrook Johanna I Internal medicine journal BACKGROUND:Quick Sepsis-related Organ Failure Assessment (qSOFA) is recommended for use by the most recent international sepsis definition taskforce to identify suspected sepsis in patients outside the intensive care unit (ICU) at risk of adverse outcomes. Evidence of its comparative effectiveness with existing sepsis recognition tools is important to guide decisions about its widespread implementation. AIM:To compare the performance of qSOFA with the adult sepsis pathway (ASP), a current sepsis recognition tool widely used in NSW hospitals and systemic inflammatory response syndrome criteria in predicting adverse outcomes in adult patients on general wards. METHODS:A retrospective observational cohort study was conducted which included all adults with suspected infections admitted to a Sydney teaching hospital between December 2014 and June 2016. The primary outcome was in-hospital mortality with two secondary composite outcomes. RESULTS:Among 2940 patients with suspected infection, 217 (7.38%) died in-hospital and 702 (23.88%) were subsequently admitted to ICU. The ASP showed the greatest ability to correctly discriminate in-hospital mortality and secondary outcomes. The area under the receiver-operating characteristic curve for mortality was 0.76 (95% confidence interval (CI): 0.74-0.78), compared to 0.64 for the qSOFA tool (95% CI: 0.61-0.67, P < 0.0001). Median time from the first ASP sepsis warning to death was 8.21 days (interquartile range (IQR): 2.29-16.75) while it was 0 days for qSOFA (IQR: 0-2.58). CONCLUSIONS:The ASP demonstrated both greater prognostic accuracy and earlier warning for in-hospital mortality for adults on hospital wards compared to qSOFA. Hospitals already using ASP may not benefit from switching to the qSOFA tool. 10.1111/imj.14746
    Initial lactate levels versus lactate clearance for predicting mortality in sepsis: A prospective observational analytical study. Lestari Mayang Indah,Sedono Rudyanto, JPMA. The Journal of the Pakistan Medical Association OBJECTIVE:Lactate is a useful prognostic marker, as its level increases in hypoxic tissue and/or during accelerated aerobic glycolysis due to excessive beta-adrenergic stimulation and decreased lactate clearance. The Surviving Sepsis Campaign Bundle 2018 Update suggested re-measurement of lactate within 2-4 hours so as to conduct/ help/administer /introduce lactate-guided resuscitation to reduce mortality due to sepsis. The aim of this study was to compare initial lactate levels and lactate clearance at 4 h of recognition of sepsis as mortality predictors in sepsis. Methods:It was a prospective study performed with ethical approval in a single tertiary care centre. Patients aged 18 years or older who were diagnosed with sepsis by the Sepsis-3 definition were included in the study while patients who were not admitted to the ICU were excluded Dropout criteria was death of pateints within 4 hours of recognition of sepsis. Baseline demographic data was obtained and subjects were treated with an hour-1 bundle and examined for initial lactate levels. At 4 hours, lactate was re-measured and patients were observed for 28 days then after Lactate clearance was calculated by the following formula: ([initial lactate - hour-4 lactate]/initial lactate) × 100. RESULTS:Of the 41 subjects included in the study; 27 died (28-day mortality --65.9%). Age, sex, diagnosis of the patient and Charlson's Comorbidities scores between survivors and non-survivors showed no significant differences. Non-survivors had higher Sequential (sepsis-related) Organ Function Assessment (SOFA) scores (11.41±3.46 versus 8.77±2.92; p=0.02). Initial lactate levels and lactate clearance did not differ in prognostic value (AUC 0.67 versus 0.5; p=0.086), but initial lactate levels of >2 mmol/L had the greatest sensitivity (81.5%). CONCLUSIONS:Initial lactate level and lactate clearance did not differ in predicting mortality in patients with sepsis.
    The role of the quick sequential organ failure assessment score (qSOFA) and modified early warning score (MEWS) in the pre-hospitalization prediction of sepsis prognosis. Usul Eren,Korkut Semih,Kayipmaz Afsin Emre,Halici Ali,Kavalci Cemil The American journal of emergency medicine OBJECTIVE:Many biomarkers and scoring systems to make clinical predictions about the prognosis of sepsis have been investigated. In this study, we aimed to assess the use of the quick sequential organ failure assessment score (qSOFA) and modified early warning score (MEWS) scoring systems in emergency health care services for sepsis to predict intensive care hospitalization and 28-day mortality. METHOD:Patients who arrived by ambulance at the Emergency Department (ED) of Dışkapı YıldırımBeyazıt Training and Research Hospital between January 2017 and December 2019, and who were diagnosed with sepsis and admitted to the hospital were included in the study. Demographic data and physiological parameters from 112 ambulance case delivery forms were recorded.QSOFA and MEWS scores were calculated from vital parameters. RESULTS:Of the 266 patients diagnosed with sepsis, 50% (n = 133) were female, and the mean age was 74.8 ± 13. The difference between the rate of intensive care (ICU) hospitalization and mortality for patients with a high MEWS and qSOFA score and patients whose MEWS and qSOFA score were lower was found to be statistically significant (p < 0.05). Thus, the criteria for MEWS and qSOFA could determine ICU hospitalization and early mortality. Those with a high MEWS value had a mortality rate approximately 1.24 times higher than those with a low MEWS value (p < 0.001, 95% CI: 1.110-1.385), while those with a high qSOFA score had a mortality rate approximately 2.0 times higher than those with a low qSOFA score (p < 0.001, 95% CI: 1.446-2.693). Those with a high MEWS were 1.34 times more likely than hose with a lower MEWS to require ICU hospitalization (p < 0.001, 95% CI: 1.1773-1.5131), while patients with a high qSOFA score were 3.21 times more likely than those with a lower qSOFA score to require ICU care (p < 0.001, 95% CI: 2.2289-4.6093). CONCLUSION:Although qSOFA and MEWS are clinical scores used to identify septic patients outside the critical care unit, we believe that patients already diagnosed with sepsis can be assessed with qSOFA and MEWS prior to hospitalization to predict intensive care hospitalization and mortality. qSOFA was found be more valuable than MEWS in determining the prognosis of pre-hospitalization sepsis. 10.1016/j.ajem.2020.09.049
    Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units. Piva Elisa,Zuin Jenny,Pelloso Michela,Tosato Francesca,Fogar Paola,Plebani Mario Clinical chemistry and laboratory medicine OBJECTIVES:Patients in Intensive Care Units (ICU) are a high-risk population for sepsis, recognized as a major cause of admission and death. The aim of the current study was to evaluate the diagnostic accuracy and prognostication of monocyte distribution width (MDW) in sepsis for patients admitted to ICU. METHODS:Between January and June 2020, we conducted a prospective observational study during the hospitalization of 506 adult patients admitted to the ICU. MDW was evaluated in 2,367 consecutive samples received for routine complete blood counts (CBC) performed once a day and every day during the study. Sepsis was diagnosed according to Sepsis-3 criteria and patients enrolled were classified in the following groups: no sepsis, sepsis and septic shock. RESULTS:MDW values were significantly higher in patients with sepsis or septic shock in comparison to those within the no sepsis group [median 26.23 (IQR: 23.48-29.83); 28.97 (IQR: 21.27-37.21); 21.99 (IQR: 19.86-24.36) respectively]. ROC analysis demonstrated that AUC is 0.785 with a sensitivity of 66.88% and specificity of 77.79% at a cut-off point of 24.63. In patients that developed an ICU-acquired sepsis MDW showed an increase from 21.33 [median (IQR: 19.47-21.72)] to 29.19 [median (IQR: 27.46-31.47)]. MDW increase is not affected by the aetiology of sepsis, even in patients with COVID-19. In sepsis survivors a decrease of MDW values were found from the first time to the end of their stay [median from 29.14 (IQR: 26.22-32.52) to 25.67 (IQR: 22.93-30.28)]. CONCLUSIONS:In ICU, MDW enhances the sepsis detection and is related to disease severity. 10.1515/cclm-2021-0192
    Review: The Emerging Role of Neutrophil Extracellular Traps in Sepsis and Sepsis-Associated Thrombosis. Chen Zhaoyuan,Zhang Hao,Qu Mengdi,Nan Ke,Cao Hanzhong,Cata Juan P,Chen Wankun,Miao Changhong Frontiers in cellular and infection microbiology Patients with sepsis commonly suffer from coagulation dysfunction and lead to the formation of thrombus. During the development of sepsis, neutrophils migrate from the circulating blood to infected tissues and mediate the formation of neutrophil extracellular traps (NETs) that kill pathogens. However, the overactivation of neutrophils can promote the formation of immunothrombosis and even cause disseminated intravascular coagulation (DIC), which damages microcirculation. The outcome of sepsis depends on early recognition and intervention, so clinical evaluation of NETs function may be a valuable biomarker for early diagnosis of sepsis. The interaction of NETs with platelets, complement, and endothelium mediates the formation of immunothrombosis in sepsis. Inhibiting the formation of NETs is also considered to be one of the potential treatments for sepsis. In this review, we will discuss the key role of neutrophils and NETs in sepsis and septic thrombosis, in order to reveal new mechanisms for thrombosis treatment of sepsis. 10.3389/fcimb.2021.653228
    Diagnostic value of neutrophil CD64, procalcitonin, and interleukin-6 in sepsis: a meta-analysis. Cong Shan,Ma Tiangang,Di Xin,Tian Chang,Zhao Min,Wang Ke BMC infectious diseases BACKGROUND:The aim of the study was to conduct a meta-analysis to evaluate the accuracy of neutrophil CD64, procalcitonin (PCT), and interleukin-6 (IL-6) as markers for the diagnosis of sepsis in adult patients. METHODS:Various databases were searched to collect published studies on the diagnosis of sepsis in adult patients using neutrophil CD64, PCT, and IL-6 levels. Utilizing the Stata SE 15.0 software, forest plots and the area under the summary receiver operating characteristic curves were drawn. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. RESULTS:Fifty-four articles were included in the study. The pooled sensitivity, specificity, and AUC of neutrophil CD64 for the diagnosis of sepsis were 0.88 (95% confidence interval [CI], 0.81-0.92), 0.88 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.91-0.96), respectively. The pooled sensitivity, specificity, and AUC of PCT for the diagnosis of sepsis were 0.82 (95% CI, 0.78-0.85), 0.78 (95% CI, 0.74-0.82), and 0.87 (95% CI, 0.83-0.89), respectively. Subgroup analysis showed that the AUC for PCT diagnosis of intensive care unit (ICU) sepsis was 0.86 (95% CI, 0.83-0.89) and the AUC for PCT diagnosis of non-ICU sepsis was 0.82 (95% CI, 0.78-0.85). The pooled sensitivity, specificity, and AUC of IL-6 for the diagnosis of sepsis were 0.72 (95% CI, 0.65-0.78), 0.70 (95% CI, 0.62-0.76), and 0.77 (95% CI, 0.73-0.80), respectively. CONCLUSIONS:Of the three biomarkers studied, neutrophil CD64 showed the highest diagnostic value for sepsis, followed by PCT, and IL-6. On the other hand, PCT showed a better diagnostic potential for the diagnosis of sepsis in patients with severe conditions compared with that in patients with non-severe conditions. 10.1186/s12879-021-06064-0
    Consumptive coagulopathy is associated with a disturbed host response in patients with sepsis. van Vught Lonneke A,Uhel Fabrice,Ding Chao,Van't Veer Cees,Scicluna Brendon P,Peters-Sengers Hessel,Klein Klouwenberg Peter M C,Nürnberg Peter,Cremer Olaf L,Schultz Marcus J,van der Poll Tom, Journal of thrombosis and haemostasis : JTH BACKGROUND:A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy. OBJECTIVES:To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis. METHODS:Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling. MEASUREMENTS AND MAIN RESULTS:Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30-day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism. CONCLUSION:A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms. 10.1111/jth.15246
    Hyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis. Wang Huabin,Zhang Lidan,Liao Wenhua,Huang Junbin,Xu Jiannan,Yang Jing,Chen Chun,He Zhijie Clinical biochemistry BACKGROUND:Sepsis is the leading cause of hospitalization and death in the intensive care unit. It is vital to identify high-risk patients with poor prognosis in the early stages of sepsis. We aimed to investigate the prognostic value of serum phosphorus levels for sepsis. METHODS:The data of 4767 patients with sepsis were collected from the Multiparameter Intelligent Monitoring in Intensive Care III database. The Locally Weighted Scatterplot Smoothing technique and Kaplan-Meier analysis were used to test the crude relationship between serum phosphorus levels and mortality or overall survival. The multivariable logistic regression was used to further analyze the relationship between serum phosphorus levels and in-hospital mortality. The subgroup analysis was performed according to renal failure, use of vasopressin and the Sequential Organ Failure Assessment (SOFA) score. RESULTS:Only hyperphosphatemia significantly correlated with in-hospital mortality [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.19-1.85], while the correlation between hypophosphatemia and in-hospital mortality was not significant (OR 0.91; 95% CI 0.70-1.19). The interactions between serum phosphorus and renal failure, use of vasopressin or the SOFA score were not significant. CONCLUSIONS:Hyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis. 10.1016/j.clinbiochem.2021.01.016
    Elevated B-type natriuretic peptide (BNP) and soluble thrombomodulin (sTM) indicates severity and poor prognosis of sepsis. Yue Lei,Deng Xiyu,Yang Mengdie,Li Xin Annals of palliative medicine BACKGROUND:To study the predictive value of B-type natriuretic peptide (BNP) and soluble thrombomodulin (sTM) in the severity stratification and prognosis evaluation of sepsis. METHODS:The clinical data of 137 sepsis patients diagnosed and treated in Sichuan Provincial People's Hospital from May 2018 to November 2020 were retrospectively analyzed. Meanwhile, 121 healthy individuals were selected as the control group. Patients with sepsis were allocated into the mild group, severe group, and shock group according to the severity. According to the 28-day prognosis, the patients were allocated into the death group and survival group. The plasma BNP and serum sTM levels in different groups were compared, and their prognostic value was evaluated. RESULTS:Patients with sepsis had significantly higher levels of BNP and sTM than the healthy control group (P<0.05). The levels of BNP and sTM in the mild group were significantly lower than those in the severe group and shock group, and both BNP and sTM were positively correlated with Acute Physiology and Chronic Health Status (APACHE) II score (r=0.595, 0.516, P<0.05). The levels of BNP and sTM in the death group were significantly higher than those in the survival group (P<0.05). The area under curve (AUC) of BNP combined with sTM was significantly greater than that of BNP or sTM alone for the prognosis of sepsis (P<0.05). When the cut-off value of BNP was 625.68 pg/mL, the sensitivity and specificity were 77.42% and 89.42%, respectively. When the cut-off value of sTM was 10.53 ng/mL, the sensitivity and specificity were 83.87% and 94.34%, respectively. CONCLUSIONS:Patients with sepsis have significantly higher serum BNP and sTM levels which are positively correlated with the severity of the disease. Both of the 2 indexes have good prognostic value, and the predictive value is higher when combined. 10.21037/apm-21-1048
    Sepsis calculator for neonatal early onset sepsis - a systematic review and meta-analysis. Deshmukh Mangesh,Mehta Shailender,Patole Sanjay The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians BACKGROUND:Over investigation and overuse of empirical antibiotics is a concern in management of neonatal early onset sepsis (EOS) using the Centers for Disease Control and Prevention guidelines. "Sepsis calculator" is a risk-based prediction model for managing neonates at risk of EOS. OBJECTIVE:To compare outcomes of neonatal EOS using of sepsis calculator versus conventional approach. METHODS:A systematic review of randomized controlled trials (RCT) and non-RCTs reporting on outcomes after implementation of sepsis calculator for EOS for neonates >34-week gestation was conducted using the Cochrane methodology. Databases PubMed, CINAHL, Embase, Cochrane Central library and Google Scholar were searched in May 2019. Primary outcomes were antibiotics usage and laboratory tests for managing EOS. Secondary outcomes included hospital admissions and readmissions, blood culture positive EOS and mortality. The level of evidence (LOE) was summarized using the GRADE guidelines. RESULTS:A total of 387 articles were retrieved after initial search. Six high quality non-RCTs fulfilled inclusion criteria. Meta-analysis (random effects model) showed that implementation of sepsis calculator was associated with reduced antibiotic usage [ = 172,385; OR = 0.22 (0.14-0.36);  < .00001; heterogeneity () = 97%, Number needed to treat (NNT): 22], laboratory tests [ = 168,432; OR = 0.14 (0.08-0.27);  < .00001;  = 99%, NNT = 8], and admissions to neonatal unit [ = 16,628; OR = 0.24 (0.11-0.51);  = .0002;  = 98%, NNT = 7]; LOE: moderate. There was no difference in mortality, culture positive EOS, and readmissions. CONCLUSION:Moderate quality evidence indicates that the implementation of a sepsis calculator was associated with reduced usage of antibiotics, laboratory tests and admission to neonatal unit with no increase in mortality and readmissions. 10.1080/14767058.2019.1649650
    Preventing sepsis; how can artificial intelligence inform the clinical decision-making process? A systematic review. Hassan Nehal,Slight Robert,Weiand Daniel,Vellinga Akke,Morgan Graham,Aboushareb Fathy,Slight Sarah P International journal of medical informatics BACKGROUND AND OBJECTIVES:Sepsis is a life-threatening condition that is associated with increased mortality. Artificial intelligence tools can inform clinical decision making by flagging patients at risk of developing infection and subsequent sepsis. This systematic review aims to identify the optimal set of predictors used to train machine learning algorithms to predict the likelihood of an infection and subsequent sepsis. METHODS:This systematic review was registered in PROSPERO database (CRD42020158685). We conducted a systematic literature review across 3 large databases: Medline, Cumulative Index of Nursing and Allied Health Literature, and Embase. Quantitative primary research studies that focused on sepsis prediction associated with bacterial infection in adults in all care settings were eligible for inclusion. RESULTS:Seventeen articles met our inclusion criteria. We identified 194 predictors that were used to train machine learning algorithms, with 13 predictors used on average across all included studies. The most prevalent predictors included age, gender, smoking, alcohol intake, heart rate, blood pressure, lactate level, cardiovascular disease, endocrine disease, cancer, chronic kidney disease (eGFR<60 mL/min), white blood cell count, liver dysfunction, surgical approach (open or minimally invasive), and pre-operative haematocrit < 30 %. All included studies used artificial intelligence techniques, with average sensitivity 75.7 ± 17.88, and average specificity 63.08 ± 22.01. CONCLUSION:The type of predictors influenced the predictive power and predictive timeframe of the developed machine learning algorithm. Predicting the likelihood of sepsis through artificial intelligence can help concentrate finite resources to those patients who are most at risk. Future studies should focus on developing more sensitive and specific algorithms. 10.1016/j.ijmedinf.2021.104457
    Serum-soluble PD-L1 may be a potential diagnostic biomarker in sepsis. Sun Shaoqiong,Chen Yang,Liu Zhaojun,Tian Rui,Liu Jialin,Chen Erzhen,Mao Enqiang,Pan Tingting,Qu Hongping Scandinavian journal of immunology To investigate whether serum-soluble PD-L1 (sPD-L1) is a potential biomarker for identifying sepsis. This study enrolled 64 septic patients, 29 patients with acute appendicitis, 33 patients with acute pancreatitis and 30 healthy volunteers. Sepsis was defined according to the Sepsis 3.0 criteria.[1] The associated clinical parameters were recorded, blood samples were collected on the first day of diagnosis, and serum sPD-L1 levels were measured using enzyme-linked immunosorbent assays. Compared with the control group, a significant increase in sPD-L1 levels was observed in patients with sepsis (n = 64). Increased sPD-L1 expression correlated strongly with increased clinical inflammatory values (CRP, PCT and WBC) and decreased immunological functional parameters (CD3 , CD4 and CD8 cell counts). The area under the ROC curve (AUC) for sPD-L1 in combination with the sequential organ failure assessment (SOFA) score was superior to the AUC for either sPD-L1 or SOFA score in regard to the diagnosis of sepsis. sPD-L1 may represent a valuable biomarker for the diagnosis of sepsis. 10.1111/sji.13049
    Knowledge of health workers relating to sepsis awareness and management in Lambaréné, Gabon. Adegbite Bayode R,Edoa Jean Ronald,Rylance Jamie,Jacob Shevin T,Kawale Paul,Adegnika Ayola A,Grobusch Martin P Acta tropica Background In 2016, the third international consensus definitions for sepsis and septic shock (Sepsis-3) task force provided revised definitions for sepsis and septic shock. This study explores knowledge regarding sepsis among health workers in Lambaréné, Gabon. Methods We conducted a self-administered questionnaire-based survey about sepsis among health workers from the referral regional hospital, the research center, and primary care health facilities in the Lambaréné region. Participants were from the referral regional hospital, the research center, and primary health care facilities. A score of one was given to each correct answer. The global score out of a possible score of twenty was calculated, and the proportion of correct responses was determined. Results A total of 115 health workers (physicians, nurses and assistant nurses) completed the questionnaire, of which 48.7% (56/115) provided a valid definition of sepsis, but 74% (85/115) had never heard about the quick Sequential Organ Failure Assessment (qSOFA) score. The proportion of correct answers was comparable across the three health profession categories. The median global score across all health workers was 11 [IQR, 9-14.5] out of 20. Physicians attained higher global scores [14 (IQR, 11-15)] than assistant nurses [11 (IQR, 8-13), P=0.007]; their global score was comparable to that of nurses. Conclusion There are considerable knowledge gaps regarding sepsis among health workers in Lambaréné, potentially impairing the prompt recognition and management of sepsis. There is a need to establish periodic up-to-date training to improve sepsis knowledge. 10.1016/j.actatropica.2021.105914
    Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes. Larsen Gitte Y,Brilli Richard,Macias Charles G,Niedner Matthew,Auletta Jeffery J,Balamuth Fran,Campbell Deborah,Depinet Holly,Frizzola Meg,Hueschen Leslie,Lowerre Tracy,Mack Elizabeth,Paul Raina,Razzaqi Faisal,Schafer Melissa,Scott Halden F,Silver Pete,Wathen Beth,Lukasiewicz Gloria,Stuart Jayne,Riggs Ruth,Richardson Troy,Ward Lowrie,Huskins W Charles, Pediatrics Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions. 10.1542/peds.2020-1434
    Validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in Internal Medicine wards; a prospective, multicenter study. Fortini Alberto,Faraone Antonio,Meini Simone,Bettucchi Michael,Longo Benedetta,Valoriani Beatrice,Forni Silvia, European journal of internal medicine BACKGROUND:Few data are available on the validity of "Sepsis-3" criteria in identifying patients with sepsis in internal medicine wards (IMWs). Real-life data about this topic and on the prevalence of sepsis in IMWs could be useful for improving hospital organization. OBJECTIVES:To assess the validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in IMWs. Secondary objectives: to evaluate the prevalence of these patients in IMWs and to compare "Sepsis-3" and "Sepsis-1" criteria. METHODS:Multicenter, prospective, observational, cohort study, carried out in 22 IMWs of Tuscany (Italy). All patients admitted to each of the study centers over a period of 21-31 days were evaluated within 48 hours; those with clinical signs of infection were enrolled. The main outcome was in-hospital mortality. RESULTS:2,839 patients were evaluated and 938 (33%) met the inclusion criteria. Patients with sepsis diagnosed according to "Sepsis-3" were 522, representing 55.6% of patients with infection and 18.4% of all patients hospitalized; they were older than those without sepsis (79.4±12.5 vs 74.6±15.2 years, p<0.001). In-hospital mortality was significantly higher in patients with sepsis compared to others (13.8% vs 4.6%; p<0.001). "Sepsis-3" criteria showed greater predictive validity for in-hospital mortality than "Sepsis-1" criteria (AUROC=0.71; 95%CI, 0.66-0.77 vs 0.60; 95%CI 0.54-0.66; p=0.0038). CONCLUSIONS:"Sepsis-3" criteria are able to identify patients with community-onset sepsis in IMWs, whose prevalence and in-hospital mortality are remarkably high. Medical departments should adapt their organization to the needs for care of these complex patients. 10.1016/j.ejim.2020.12.025
    Silent existence of eosinopenia in sepsis: a systematic review and meta-analysis. Lin Yao,Rong Jiabing,Zhang Zhaocai BMC infectious diseases BACKGROUND:Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for patients susceptible to sepsis. Eosinopenia has been identified as a potential biomarker of sepsis in the past decade. However, its clinical application progress is slow and its recognition is low. Recent studies have again focused on the potential association between Eosinopenia and severe infections. This study analyzed the efficacy of Eosinopenia as a biomarker for diagnosis of sepsis and its correlation with pathophysiology of sepsis. METHOD:The protocol for this meta-analysis is available in PROSPERO (CRD42020197664). We searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials CENTRAL databases to identify studies that met the inclusion criteria. Two authors performed data extraction independently. The pooled outcomes were calculated by TP (true positive), FP (false positive), FN (false negative), TN (true negative) by using bivariate meta-analysis model in STATA 14.0 software. Meanwhile, possible mechanisms of sepsis induced Eosinopenia was also analyzed. RESULTS:Seven studies were included in the present study with a total number of 3842 subjects. The incidence of Eosinopenia based on the enrolled studies varied from 23.2 to 92.7%. For diagnosis of sepsis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of Eosinopenia were 0.66 (95%CI [0.53-0.77]), 0.68 (95%CI [0.56-0.79]), 2.09 (95%CI [1.44-3.02]), 0.49 (95%CI [0.34-0.71]) and 4.23 (95%CI [2.15-8.31]), respectively. The area under the summary receiver operator characteristic curve (SROC) was 0.73 (95%CI [0.68-0.76]). Meta-regression analysis revealed that no single parameter accounted for the heterogeneity of pooled outcomes. For each subgroup of different eosinopenia cutoff values (50, 40, ≤25, 100), the sensitivity was 0.61, 0.79, 0.57, 0.54, and the specificity was 0.61, 0.75, 0.83, 0.51, respectively. CONCLUSIONS:Our findings suggested that Eosinopenia has a high incidence in sepsis but has no superiority in comparison with conventional biomarkers for diagnosis of sepsis. However, eosinopenia can still be used in clinical diagnosis for sepsis as a simple, convenient, fast and inexpensive biomarker. Therefore, further large clinical trials are still needed to re-evaluate eosinopenia as a biomarker of sepsis. 10.1186/s12879-021-06150-3
    Early lactate measurements for predicting in-hospital mortality in paediatric sepsis. Jaiswal Priyanka,Dewan Pooja,Gomber Sunil,Banerjee Basu Dev,Kotru Mrinalini,Malhotra Rajeev Kumar,Tyagi Vipin Journal of paediatrics and child health AIM:We compared the performance of plasma lactate with high-sensitivity C-reactive protein (hs-CRP), and paediatric sepsis-related organ failure assessment (pSOFA) score for predicting mortality in septic children. METHODS:Serial plasma lactate and hs-CRP levels and pSOFA score was assessed during early hospital stay in septic children. RESULTS:Out of 149 participants, 45 died. Plasma lactate at 0 h and 6 h was significantly higher, and lactate clearance was significantly lower in non-survivors. The optimal cut-off of plasma lactate at 6h for identifying mortality was 2.5 mmol/L (sensitivity 85% and specificity 74%). pSOFA score had the best predictive ability for mortality (AUC 0.89) followed by hs-CRP at 0 h (AUC 0.86), hs-CRP at 48 h (AUC 0.83), plasma lactate levels at 6 h (AUC 0.83), and plasma lactate at 0 h (AUC 0.67). CONCLUSION:pSOFA score, hs-CRP and hyperlactemia at 6 h can identify septic children at risk of dying. 10.1111/jpc.15028
    Pivotal role of endothelial cell autophagy in sepsis. Li Yuexian,Suo Liangyuan,Fu Zhiling,Li Guoqing,Zhang Jin Life sciences Sepsis is a fatal organ dysfunction resulting from a disordered host response to infection. Endothelial cells (ECs) are usually the primary targets of inflammatory mediators in sepsis; damage to ECs plays a pivotal part in vital organ failure. In recent studies, autophagy was suggested to play a critical role in the ECs injury although the mechanisms by which ECs are injured in sepsis are not well elucidated. Autophagy is a highly conserved catabolic process that includes sequestrating plasma contents and transporting cargo to lysosomes for recycling the vital substrates required for metabolism. This pathway also counteracts microbial invasion to balance and retain homeostasis, especially during sepsis. Increasing evidence indicates that autophagy is closely associated with endothelial function. The role of autophagy in sepsis may or may not be favorable depending upon conditions. In the present review, the current knowledge of autophagy in the process of sepsis and its influence on ECs was evaluated. In addition, the potential of targeting EC autophagy for clinical treatment of sepsis was discussed. 10.1016/j.lfs.2021.119413
    Diagnostic performance of biomarkers in maternal sepsis: A prospective observational study. Katoch Tanvi,Singh Anju,Suri Vanita,Sethi Sunil,Sachdeva Naresh,Naseem Shano International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics OBJECTIVES:Maternal sepsis is a life-threatening condition. Biomarkers have been found to be useful in early detection of sepsis in the critical care setting. We aimed to determine the diagnostic performance of different biomarkers such as procalcitonin, C-reactive protein (CRP), absolute eosinophil count, and activated partial thromboplastin time (aPTT) in maternal sepsis. METHODS:A total of 35 patients were enrolled in this prospective observational study. Patients with suspected sepsis were evaluated for multi-organ dysfunction. The blood samples for testing of these biomarker levels were obtained at the time of enrollment in the study (day 1), and on day 3 and day 7. Trends of each marker were followed and correlated with the clinical picture. RESULTS:Of 35 enrolled patients, 30 completed the study. Among these, 18 had sepsis and 12 were designated as without sepsis. Sensitivities of procalcitonin, CRP, aPTT, and absolute eosinophil count were 83.33%, 77.78%, 55.56%, and 58.82% whereas their specificities were 66.67%, 75.0%, 100%, and 75%, respectively. Area under the curve was highest for procalcitonin (0.813) followed in decreasing order by CRP (0.778), aPTT (0.731), and eosinophil count (0.642), respectively. CONCLUSION:Procalcitonin and CRP may be used as a valuable adjunct in the clinical stepwise approach for the prompt diagnosis of maternal sepsis. 10.1002/ijgo.13525
    The association between clinical and biochemical characteristics of late-onset sepsis and bronchopulmonary dysplasia in preterm infants. Ebrahimi Melania E,Romijn Michelle,Vliegenthart Roos J S,Visser Douwe H,van Kaam Anton H,Onland Wes European journal of pediatrics Studies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known: • Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia • This association is mainly shown in infants with a positive blood culture What is New: • This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia • The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia. 10.1007/s00431-021-03981-9
    Predictive Accuracy of the Quick Sepsis-related Organ Failure Assessment Score in Brazil. A Prospective Multicenter Study. Machado Flavia R,Cavalcanti Alexandre B,Monteiro Mariana B,Sousa Juliana L,Bossa Aline,Bafi Antonio T,Dal-Pizzol Felipe,Freitas Flavio G R,Lisboa Thiago,Westphal Glauco A,Japiassu Andre M,Azevedo Luciano C P, American journal of respiratory and critical care medicine Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity. To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity. We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis. Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3). A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493). 10.1164/rccm.201905-0917OC
    Septicaemia, thrombocytopaenia and thrombosis. Lever Elliott,Day John,Islam Mohammed British journal of hospital medicine (London, England : 2005) 10.12968/hmed.2017.78.8.468
    Neonatal septicemia at intensive care unit, Ayder Comprehensive Specialized Hospital, Tigray, North Ethiopia: Bacteriological profile, drug susceptibility pattern, and associated factors. Weldu Yemane,Naizgi Mulugeta,Hadgu Amanuel,Desta Abraham Aregay,Kahsay Amlsha,Negash Letemichael,Hailu Genet Gebrehiwet,Wasihun Araya Gebreyesus PloS one BACKGROUND:Neonatal septicemia is a life threatening medical emergency that requires timely detection of pathogens with urgent rational antibiotics therapy. METHODS:A cross-sectional study was conducted between March 2017 to September 2018 among 317 septicemia suspected neonates at neonatal intensive care unit, Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, North Ethiopia. A 3 mL of blood was collected from each participant. Identification of bacterial species was done using the standard microbiological techniques. Antibiotic sensitivity test was done using disk diffusion method. Data were entered and analyzed using computer software SPSS version 22. Bivariate and multivariate regression analysis was applied to determine the association between variables. RESULTS:Of the 317 (190 male and 127 female) neonates, 116 (36.6%) were found to be with culture proven septicemia. Klebsiella species were the predominant etiologic agents. Length of hospital stay (AOR (adjusted odds ratio) = 3.65 (2.17-6.13), p < 0.001) and low birth weight (AOR = 1.64 (1.13-2.78), p = 0.04) were the factors associated with neonatalsepticemia. Most isolates showeda frightening drug resistance rate to the commonly used antimicrobial drugs. K. pneumoniae, E. coli, Enterobacter and Citrobacter species were 57% to100% resistant to ceftazidime, ceftriaxone, gentamycin, amoxacillin-clavulunic acid and ampicillin. All, 9 (100%) isolates of S. aureus were resistant to oxacilline, ampicillin,erythromycin and gentamycin. Furthermore, 55.6% S. aureus isolates were Methicillin Resistant Staphylococcus aureus. CONCLUSION:Neonaltal septicemia is found to be significantly high in the present study. As most of the isolates are potentially related to hospital acquired infections, prevention and control policy should have to be more strengthening in the neonatal intensive care unit. 10.1371/journal.pone.0235391
    Real-world use of procalcitonin and other biomarkers among sepsis hospitalizations in the United States: A retrospective, observational study. Gluck Eric,Nguyen H Bryant,Yalamanchili Kishore,McCusker Margaret,Madala Jaya,Corvino Frank A,Zhu Xuelian,Balk Robert PloS one BACKGROUND:Sepsis management guidelines endorse use of biomarkers to support clinical assessment and treatment decisions in septic patients. The impact of biomarkers on improving patient outcomes remains uncertain. METHODS:Retrospective observational study of adult sepsis discharges between January 1, 2012, and December 31, 2015, from Premier Healthcare Database hospitals. Sepsis was defined by an All Patients Refined Diagnosis-Related Group code of 720 (septicemia and disseminated infections). Use of four biomarker strategies was evaluated based on hospital records: (i) >1 procalcitonin (PCT), (ii) 1 PCT, (iii) no PCT but ≥1 C-reactive protein (CRP) and/or lactate and (iv) no sepsis biomarkers. Associations between biomarker use and clinical and cost outcomes were examined. The primary outcome was impact of biomarker strategy on hospital costs per day. RESULTS:Among 933,591 adult sepsis discharges during the study period, 731,392 (78%) had biomarker tests ordered. In multivariable analyses, discharges with >1 PCT had higher hospital costs per day ($1,904; 95% confidence interval [CI] $1,896-$1,911) compared with discharges with no sepsis biomarkers ($1,606; 95% CI $1,658-$1,664). Discharges with >1 PCT also had greater illness severity and antimicrobial exposure compared with other biomarker-use groups. The adjusted odds of dying during hospital stay compared with being discharged were significantly lower for sepsis discharges with >1 PCT (0.64; 95% CI 0.61-0.67) and 1 PCT (0.88; 95% CI 0.85-0.91) compared with no sepsis biomarker use. The proportion of discharges with ≥1 PCT increased almost six-fold during the study; use of other biomarkers remained constant. CONCLUSIONS:Between 2012 and 2015, PCT use among sepsis discharges increased six-fold while lactate and CRP use remained unchanged. PCT use was associated with decreased odds of in-hospital mortality but increased hospital costs per day. Serial biomarker monitoring may be associated with improved patient outcomes in the most critically ill septic patients. 10.1371/journal.pone.0205924
    [Value of procalcitonin in predicting the severity and prognosis of neonates with septicemia]. Zhang J,Qu D,Ren X X,Cui X D,Fu J Zhonghua yi xue za zhi To explore the value of procalcitonin(PCT) in predicting the severity and prognosis of neonates with septicemia. The clinical data of the hospitalized neonates over the age of 72 hours with double positive blood cultures from December 1st, 2011 to September 30, 2017 at the neonatal intensive care unit of Children's Hospital Affiliated to Capital Institute of Pediatrics was analyzed retrospectively. A total of 75 neonates were included in the study. There was a significant negative correlation between PCT and neonatal critical illness score (=-0.440, <0.05). Among the groups of non-critical, critical and extremely critical, the levels of PCT had significant difference [0.27(0.10-2.55), 4.34(1.24-20.32), 19.49(1.92-106.49)μg/L, =20.717, <0.01]. At a cut-off point of 0.56 μg/L, PCT showed 88.6% sensitivity and 61.3% specificity for critical group diagnosis, with optimal area under the curve of 0.804 (<0.05). At a cut-off point of 11.45 μg/L, PCT showed 65.2% sensitivity and 82.7% specificity for extremely critical group diagnosis, with optimal area under the curve of 0.735 (<0.05). Among the groups of none organ dysfunction, single organ dysfunction and shock or multiple organ dysfunction, the levels of PCT had significant difference[0.10(0.43-2.56), 3.18(0.67-20.95), 18.97(1.92-82.90) μg/L, =20.299, <0.01]. At a cut-off point of 2.64 μg/L, PCT showed 70.0% sensitivity and 77.1% specificity for single organ dysfunction diagnosis, with optimal area under the curve of 0.793 (<0.05). At a cut-off point of 9.06 μg/L, PCT showed 61.3% sensitivity and 86.4% specificity for shock or multiple organ dysfunction diagnosis, with optimal area under the curve of 0.782 (<0.05). PCT levels were significantly higher in the death group than the survival group. At a cut-off point of 75.65 μg/L, PCT showed 80.0% sensitivity and 90.0% specificity for the judgment of death, with optimal area under the curve of 0.886 (<0.05). C-reactive protein (CRP), white blood cell (WBC) and neutrophil lymphocyte ratio (NLR) had no significant difference in the severity and the degree of organ dysfunction of neonates with septicemia(all >0.05). Compared to CRP, WBC and NLR, PCT has high value in predicting the severity, the degree of organ dysfunction and the prognosis of neonates with septicemia. 10.3760/cma.j.issn.0376-2491.2018.16.016
    Curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP and hs-CRP. Xu Y-B,Ouyang Y,Zhao D European review for medical and pharmacological sciences OBJECTIVE:To explore the curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP, and hs-CRP, so as to provide references for clinical treatment. PATIENTS AND METHODS:181 patients with neonatal septicemia admitted to Huangshi Maternity and Child Health Hospital from April 2012 to August 2014 were selected as the study subjects. Patients treated with vancomycin combined with gamma globulin were selected as group A (96 cases) and those treated with cefotaxime combined with gamma globulin were selected as group B (85 cases). The improvement time of clinical symptoms (milk rejection, nervous system symptoms, body temperature), hospital stays, mortality, medicine curative effects, adverse reactions, complications, and levels of serum CRP, PCT, and hs-CRP of patients before and after treatment were compared between the two groups. RESULTS:The improvement time of clinical symptoms like body temperature, milk rejection, and neurological symptoms, as well as hospital stays in group A were lower than those in group B (p<0.05); the total effective rate of medicine curative effects in group B was better than that in group A (p<0.05); there was no significant difference in levels of serum CRP, PCT, and hs-CRP between the two groups before treatment (p>0.05); after treatment, levels of serum CRP, PCT, and hs-CRP in both groups decreased significantly, and levels of serum CRP, PCT, and hs-CRP in group B decreased more significantly than those in group A (p<0.05). CONCLUSIONS:Cefotaxime combined with gamma globulin in the treatment of patients with neonatal septicemia has short improvement time in clinical symptoms, high total effective rate of drugs, low mortality, fewer adverse reactions and complications, and can significantly reduce levels of serum CRP, PCT, and hs-CRP, which is worthy of further promotion and application in clinical practice. 10.26355/eurrev_202004_21031
    Clinical analysis and examination of neonatal sepsis. Liu Zhihua,Feng Jia,Shi Lili JPMA. The Journal of the Pakistan Medical Association OBJECTIVE:The purpose of this study is to analyze the different clinical manifestations of neonatal sepsis, the related factors leading to neonatal complications, and the related factors of common complications, so as to provide a theoretical basis and logical proof for the treatment of neonatal sepsis. METHODS:This article collects clinical data of 110 cases of septicaemic neonates, compare the clinical characteristics, general conditions, pathogen distribution, laboratory test data of two groups of patients with septicaemic, and conduct statistics and analysis. RESULTS:The results showed that among 110 patients, there were 53 (48%) cases of premature septicaemic and 9 (8%) cases were infected during pregnancy. There were 7 (6%) cases of amniotic fluid contamination. There were 26(23%) cases of risk factors in the womb. 25 (23%) cases of children with multiple symptoms., The positive rates of white blood cell and platelet examination, c-reactive protein examination and neutrophil rod-nucleus/neutrophil examination were 59.64%, 38.77%, 38.6% and 5.66% respectively. Procalcitonin level was positively correlated with c-reactive protein (P<0.01, r=0.7). Among them, 6 (5.45%) cases were positive in blood culture, including 3 (2.72%) cases of staphylococcus epidermidis, 2(1.81%)cases of staphylococcus aureus and 1(0.90%)case of escherichia coli. CONCLUSIONS:The clinical manifestations of neonatal sepsis are relatively concealed, and antibiotics are used reasonably in the early treatment process to deal with the symptoms of the disease and promote the improvement of the treatment effect.
    Pediatric Sepsis: A Primer for the Pediatrician. Conway Edward E Pediatric annals Sepsis is the body's systemic response to infection and is a serious health care concern that affects neonatal, pediatric, and adult populations worldwide. Severe sepsis (sepsis that has progressed to cellular dysfunction and organ damage or evidence of hypoperfusion) and septic shock (sepsis with persistent hypotension despite adequate fluid resuscitation) are still associated with high mortality rates despite improvements in the management of infectious processes. The cellular processes that occur as a result of the inflammatory response in sepsis, including impaired perfusion and microcirculatory coagulation, can lead to organ system dysfunction. Early recognition of sepsis can help prompt treatment to improve patient care. Current pediatric guidelines emphasize early recognition, aggressive fluid resuscitation, and administration of antibiotics within the first hour for a better outcome. The practitioner needs to always be mindful of the possibility of sepsis when examining a patient with potential symptoms. [Pediatr Ann. 2018;47(7):e292-e299.]. 10.3928/19382359-20180620-02
    [Predictive factors for poor prognosis of neonates with early-onset sepsis]. Chen Jie,Yu Jia-Lin Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the predictive factors for poor prognosis of neonates with early-onset sepsis (EOS). METHODS:The clinical data of 371 neonates with EOS were collected. According to prognosis, they were divided into a good prognosis group with 264 neonates and a poor prognosis group with 107 neonates. The two groups were compared in terms of perinatal conditions, clinical manifestations, laboratory markers, comorbidities, and treatment process. Multivariate logistic regression analysis was used to investigate the predictive factors for poor prognosis of EOS. RESULTS:The poor prognosis group had significantly lower birth weight and gestational age than the good prognosis group (P<0.05). Compared with the good prognosis group, the poor prognosis group had significantly higher proportions of preterm neonates, low birth weight neonates, very low birth weight neonates and twins (P<0.05), as well as a significantly higher proportion of mothers who used hormone or antibiotics before delivery (P<0.05). Compared with the good prognosis group, the poor prognosis group had significantly higher incidence rates of poor response and respiratory hypofunction (P<0.05) and a significantly lower incidence rate of jaundice (P<0.05). Compared with the good prognosis group, the poor prognosis group had significantly higher incidence rates of white blood cell count <5×10/L, platelet count <100×10/L, anemia, coagulation disorder, renal dysfunction, liver impairment, hypoproteinemia, and hypoglycemia (P<0.05). The poor prognosis group had significantly higher incidence rates of neonatal respiratory distress syndrome, pulmonary hemorrhage, necrotizing enterocolitis, intraventricular hemorrhage, brain injury, pulmonary hypertension, and shock than the good prognosis group (P<0.05). Compared with the good prognosis group, the poor prognosis group had significantly longer length of hospital stay and course of treatment with antibiotics (P<0.05) and a significantly higher proportion of neonates receiving mechanical ventilation or vasoactive agents (P<0.05). The multivariate logistic regression analysis showed that very low birth weight (OR=41.734), necrotizing enterocolitis (OR=12.669), brain injury (OR=8.372), shock (OR=5.889), mechanical ventilation (OR=5.456), and liver impairment (OR=4.075) were independent predictive factors for poor prognosis of neonates with EOS (P<0.05). CONCLUSIONS:Very low birth weight, mechanical ventilation, necrotizing enterocolitis, brain injury, shock, and liver impairment have a certain value in predicting the poor prognosis of neonates with EOS.
    A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function. Onishi Tomoko,Nogami Keiji,Ishihara Takashi,Inoue Satoki,Kawaguchi Masahiko,Nishio Kenji,Fukushima Hidetada,Kobayashi Hiroshi,Amano Itsuto,Nishikubo Toshiya,Yamasaki Masaharu,Kasahara Masato,Shima Midori Thrombosis and haemostasis BACKGROUND: The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin-antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. METHODS: Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma. RESULTS: CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min - max: 0.10 - 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 - 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 - 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 - 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios ( = 0.55,  < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios ( = 0.71,  < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant. CONCLUSION: A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals. 10.1055/s-0040-1713890
    Prognostic Value of Ionized Calcium Levels in Neonatal Sepsis. Liu Yalan,Chai Yannan,Rong Zhihui,Chen Yan Annals of nutrition & metabolism BACKGROUND:Despite recent advances in the treatment of neonatal infection, mortality rates and comorbidities associated with neonatal sepsis remain high. Hypocalcemia has been reported in critically ill patients, especially in as-sociation with sepsis. However, the importance of hypo-calcemia in neonatal sepsis has not been explored in detail. OBJECTIVES:The purpose of this study was to evaluate the prognostic value of hypocalcemia in neonatal sepsis patients and to identify the risk factors associated with sepsis-related mortality. METHODS:This retrospective study examined perinatal data from patients in a level IV neonatal in-tensive care unit between January 2010 and June 2016. Univariate analysis was performed to understand the differences in clinical and laboratory characteristics between patients with and without neonatal sepsis. Neonates with sepsis were further stratified as having ionized hypocalcemia (if serum ionized calcium [iCa] <1.0 mmol/L) or not. Uni- and multivariate logistic regression analyses were utilized to evaluate the predictive potential of iCa for identifying sepsis-related mortality. RESULTS:A total of 472 neonates were enrolled in this study, including 169 neonates diagnosed with culture-proven sepsis and 303 neonates without infection (control group). The comparison of neonates with and without sepsis highlighted significant differences in levels of iCa (0.97 ± 0.26 vs. 1.12 ± 0.25 mmol/L), magnesium (0.75 ± 0.22 vs. 0.89 ± 0.12 mmol/L), and phosphate (2.26 ± 1.08 vs. 1.65 ± 0.85 mmol/L; all p < 0.001). When neonates with sepsis were stratified into 2 subgroups based on serum iCa, neonates with hypocalcemia showed higher rates of organ dysfunction than those with normal iCa, as well as higher rates of cardiovascular system dysfunction (37.35 vs. 17.44%), renal dysfunction (34.94 vs. 30.95%), disseminated intravascular coagulation (26.51 vs. 11.63%), and seizure (16.04 vs. 5.8%; all p < 0.05). Among all neonates who had sepsis, the mortality rate was 13.61%, and this rate was higher among neonates with hypocalcemia than among those with normal iCa (20.48 vs. 6.98%, p < 0.05). Uni- and multivariate analyses showed that acidosis, hypoalbuminemia, hypocalcemia, and hyperphosphatemia were independent prognostic markers of sepsis-related mortality. In receiver-operating characteristic curve analysis, the areas under the curve were 0.70 (95% CI 0.624-0.768; p = 0.0004), 0.74 (95% CI 0.671-0.808; p < 0.0001), 0.73 (95% CI 0.653-0.792; p = 0.0002), and 0.67 (95% CI 0.59-0.737; p = 0.0154) for serum albumin, iCa, phosphate, and acidosis, respectively. Based on these findings, we developed a nomogram to predict sepsis-related mortality. CONCLUSIONS:Hypocalcemia is common in neonates with sepsis and is significantly associated with organ dysfunction and sepsis-related mortality. 10.1159/000508685
    Antibiotic regimens for late-onset neonatal sepsis. Korang Steven Kwasi,Safi Sanam,Nava Chiara,Greisen Gorm,Gupta Munish,Lausten-Thomsen Ulrik,Jakobsen Janus C The Cochrane database of systematic reviews BACKGROUND:Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. OBJECTIVES:To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. SEARCH METHODS:We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA:We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. DATA COLLECTION AND ANALYSIS:Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. MAIN RESULTS:We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. AUTHORS' CONCLUSIONS:Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted. 10.1002/14651858.CD013836.pub2
    Emergence of OXA-232-producing hypervirulent Klebsiella pneumoniae ST23 causing neonatal sepsis. Mukherjee Subhankar,Naha Sharmi,Bhadury Punyasloke,Saha Bijan,Dutta Moumita,Dutta Shanta,Basu Sulagna The Journal of antimicrobial chemotherapy 10.1093/jac/dkaa080
    Increased surfactant protein-D levels in the airways of preterm neonates with sepsis indicated responses to infectious challenges. Mackay Rose-Marie A,Townsend J Paul,Calvert Jennifer,Anthony Mark,Wilkinson Andrew R,Postle Anthony D,Clark Howard W,Todd David A Acta paediatrica (Oslo, Norway : 1992) AIM:Sepsis is multifactorial and potentially devastating for preterm neonates. Changes in surfactant protein-D (SP-D), phosphatidylcholine (PC) and PC molecular species during infection may indicate innate immunity or inflammation during sepsis. We aimed to compare these important pulmonary molecules in ventilated neonates without or with sepsis. METHODS:Endotracheal aspirates were collected from preterm neonates born at 23-35 weeks and admitted to the neonatal intensive care unit at the John Radcliffe Hospital, Oxford, UK, from October 2000 to March 2002. Samples were collected at one day to 30 days and analysed for SP-D, total PC and PC molecular species concentrations using enzyme-linked immunosorbent assay and mass spectrometry. RESULTS:We found that 8/54 (14.8%) neonates developed sepsis. SP-D (p < 0.0001), mono- and di-unsaturated PC were significantly increased (p = 0.05), and polyunsaturated PC was significantly decreased (p < 0.01) during sepsis compared to controls. SP-D:PC ratios were significantly increased during sepsis (p < 0.001), and SP-D concentrations were directly related to gestational age in neonates with sepsis (r  = 0.389, p < 0.01). CONCLUSION:Increased SP-D levels and changes in PC molecular species during sepsis were consistent with direct or indirect pulmonary inflammatory processes. Very preterm neonates we able to mount an acute inflammatory innate immune response to infectious challenges, despite low levels of surfactant proteins at birth. 10.1111/apa.14630
    The practice of blood volume submitted for culture in a neonatal intensive care unit. Singh Moni Pankhuri,Balegar V Kiran Kumar,Angiti Rajeshwar Reddy Archives of disease in childhood. Fetal and neonatal edition BACKGROUND:Neonatal sepsis is the leading cause of mortality and morbidity in neonatal intensive care units. The volume of blood taken for culture remains one of the most important factors in isolating microorganisms. OBJECTIVES:To evaluate the impact of the intervention on the blood volume submitted for culture and to identify factors influencing the volume as determined by the phlebotomist. METHODS:Blood culture volume was determined by weighing the culture bottle before and immediately after blood inoculation. A 3-month preintervention audit revealed that in 126/130 samples (96.9%), the volume of blood submitted was suboptimal. Multiple intervention measures were instituted, and volume was monitored over the next 9 months. RESULTS:637 blood culture samples were included in the study, 130 were in preintervention and 507 were in postintervention epochs. Following the intervention, suboptimal volume samples reduced from 96.9% (126/130 samples) to 25% (126/507 samples), p<0.0001 and the median (IQR) sample volume improved from 0.36 (0.23) ml to 0.9 (0.27) ml, p<0.0001. Poor blood flow was identified as the most common reason for an inadequate sample. CONCLUSION:The study underscores the role of educational intervention in improving the blood culture volume in newborn infants. Poor backflow from the cannula is an important cause of inadequate volume collection. 10.1136/archdischild-2019-318080
    Effect of gestational age on the epidemiology of late-onset sepsis in neonatal intensive care units - a review. Afonso Elsa Da Palma,Blot Stijn Expert review of anti-infective therapy INTRODUCTION:Neonatal sepsis is a major cause of morbidity and mortality. Late-onset sepsis affects a significant percentage of infants admitted to the neonatal intensive care unit (NICU). Most affected newborns are preterm or low birth weight, but late-onset sepsis also affects late preterm and term infants. Understanding how gestational age affects the epidemiology of late-onset sepsis can be of use when defining strategies for its prevention and clinical management in NICU. Areas covered: Available evidence suggests the incidence and mortality of late-onset sepsis is higher in preterm and VLBW infants, but pathogen distribution and risk exposure is similar across all infants admitted to NICU. More research is required for late-onset sepsis in late preterm and term infants admitted to NICU. There is some research insight on the impact of gut bacteria in the epidemiology of Gram-negative sepsis, which could benefit from further dedicated studies. Expert commentary: Understanding the manner in which some infants develop severe sepsis and others don't and what the long-term outcomes are is fundamental to guide management strategies. Further research should focus both on infants' characteristics and on pathogenic processes. The ultimate goal is to be able to design guidelines for prevention and management of sepsis that are adapted to a varied neonatal population. 10.1080/14787210.2017.1379394
    Implementation of a clinical guideline to decrease laboratory tests in newborns evaluated for early onset sepsis. Le C N,Sauer C W,Law C,Proudfoot J A,Song R S Journal of neonatal-perinatal medicine BACKGROUND:Creation of a clinical guideline to reduce the number of complete blood counts (CBCs) obtained on healthy term infants for early onset sepsis (EOS) evaluation secondary to maternal chorioamnionitis. METHODS:A clinical guideline was introduced at four neonatal intensive care units (NICU) to reduce laboratory tests during EOS evaluation. Measures include frequency and timing of CBCs, culture negative sepsis, length of stay, and readmission rate. RESULTS:Mean number of CBCs per patient significantly decreased (2.31±0.62 versus 1.52±0.65) without increasing trends for patients with culture negative sepsis, length of stay, or re-admission. CONCLUSION:The clinical guideline demonstrated a significant reduction in the number of CBCs obtained in well-appearing infants admitted to the NICU secondary to maternal chorioamnionitis. 10.3233/NPM-180181
    Early-onset Streptococcus Pneumoniae-Induced Neonatal Sepsis. Díaz Martín Cristina,Marrero Pérez Carmen Luz,Martín Fumero Lorenzo,Torres Moreno Alejandro,de Quirós Iván Archivos de bronconeumologia 10.1016/j.arbres.2020.05.011
    Management of Neonates Born at ≥35 0/7 Weeks' Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Puopolo Karen M,Benitz William E,Zaoutis Theoklis E, , Pediatrics The incidence of neonatal early-onset sepsis (EOS) has declined substantially over the last 2 decades, primarily because of the implementation of evidence-based intrapartum antimicrobial therapy. However, EOS remains a serious and potentially fatal illness. Laboratory tests alone are neither sensitive nor specific enough to guide EOS management decisions. Maternal and infant clinical characteristics can help identify newborn infants who are at risk and guide the administration of empirical antibiotic therapy. The incidence of EOS, the prevalence and implications of established risk factors, the predictive value of commonly used laboratory tests, and the uncertainties in the risk/benefit balance of antibiotic exposures all vary significantly with gestational age at birth. Our purpose in this clinical report is to provide a summary of the current epidemiology of neonatal sepsis among infants born at ≥35 0/7 weeks' gestation and a framework for the development of evidence-based approaches to sepsis risk assessment among these infants. 10.1542/peds.2018-2894
    Treatment of neonatal sepsis with intravenous immune globulin. ,Brocklehurst Peter,Farrell Barbara,King Andrew,Juszczak Edmund,Darlow Brian,Haque Khalid,Salt Alison,Stenson Ben,Tarnow-Mordi William The New England journal of medicine BACKGROUND:Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality. METHODS:At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years. RESULTS:There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events. CONCLUSIONS:Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis. 10.1056/NEJMoa1100441
    Role of C-Reactive Protein for Late-Onset Neonatal Sepsis. Burstein Brett,Beltempo Marc,Fontela Patricia S JAMA pediatrics 10.1001/jamapediatrics.2020.2129
    Use of an Early Onset-Sepsis Calculator to Decrease Unnecessary NICU Admissions and Increase Exclusive Breastfeeding. Bridges Margie,Pesek Elizabeth,McRae Michele,Chabra Shilpi Journal of obstetric, gynecologic, and neonatal nursing : JOGNN OBJECTIVE:To evaluate the effects of use of the Kaiser Neonatal Early-Onset Sepsis Calculator (NEOSC) on NICU admissions, laboratory testing, antibiotic exposure, and exclusive breastfeeding (EBF) rates in full-term neonates exposed to chorioamnionitis. DESIGN:Quality improvement project with review of retrospective data. SETTING/LOCAL PROBLEM:In this single-site, community hospital with approximately 4,000 births per year, all neonates exposed to chorioamnionitis required NICU admission, laboratory evaluation, and empiric antibiotics. PARTICIPANTS:Term neonates born to mothers diagnosed with chorioamnionitis identified through the International Classification of Diseases, Tenth Revision codes based on the discharge diagnosis. INTERVENTION/MEASUREMENTS:The baseline retrospective analysis included calculation of sepsis risk with the Kaiser NEOSC through a chart review of neonates exposed to chorioamnionitis from January 1, 2015, to December 31, 2016. We compared the risk for sepsis with actual laboratory testing and antibiotic use and examined EBF before implementation of the use of the NEOSC. Implementation began January 2017; postintervention data were examined at 6 months and 1 year. All cases of neonates exposed to chorioamnionitis after the intervention were reviewed for use of the NEOSC, NICU admission/readmission for sepsis, laboratory testing, use of antibiotics, and EBF. RESULTS:In the 12 months after NEOSC use was implemented, NICU admissions, laboratory testing, and antibiotic use decreased. Among all neonates exposed to chorioamnionitis after implementation (N = 74), 68 (93%) were not admitted to the NICU, and only 8 (11%) required laboratory evaluation. Rates of EBF in neonates exposed to chorioamnionitis increased from less than 10% to greater than 50% after implementation. The length of the NICU stay for neonates exposed to chorioamnionitis decreased from an average of 138 to 12 days with no negative consequences. CONCLUSION:Most neonates exposed to chorioamnionitis appeared well and did not require NICU admission, laboratory testing, or antibiotic therapy. Rates of EBF improved after use of NEOSC was implemented. The practice change helped prevent adverse consequences, such as painful interventions and separation of the mother and neonate. No neonates were readmitted for sepsis. 10.1016/j.jogn.2019.01.009
    Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections. Carl Mike A,Ndao I Malick,Springman A Cody,Manning Shannon D,Johnson James R,Johnston Brian D,Burnham Carey-Ann D,Weinstock Erica Sodergren,Weinstock George M,Wylie Todd N,Mitreva Makedonka,Abubucker Sahar,Zhou Yanjiao,Stevens Harold J,Hall-Moore Carla,Julian Samuel,Shaikh Nurmohammad,Warner Barbara B,Tarr Phillip I Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Late-onset sepsis is a major problem in neonatology, but the habitat of the pathogens before bloodstream invasion occurs is not well established. METHODS:We examined prospectively collected stools from premature infants with sepsis to find pathogens that subsequently invaded their bloodstreams, and sought the same organisms in stools of infants without sepsis. Culture-based techniques were used to isolate stool bacteria that provisionally matched the bloodstream organisms, which were then genome sequenced to confirm or refute commonality. RESULTS:Of 11 children with late-onset neonatal bloodstream infections, 7 produced at least 1 stool that contained group B Streptococcus (GBS), Serratia marcescens, or Escherichia coli before their sepsis episode with provisionally matching organisms. Of 96 overlap comparison subjects without sepsis temporally associated with these cases, 4 were colonized with provisionally matching GBS or S. marcescens. Of 175 comparisons of stools from randomly selected infants without sepsis, 1 contained a GBS (this infant had also served as an overlap comparison subject and both specimens contained provisionally matching GBS). Genome sequencing confirmed common origin of provisionally matching fecal and blood isolates. The invasive E. coli were present in all presepticemic stools since birth, but gut colonization with GBS and S. marcescens occurred closer to time of bloodstream infection. CONCLUSIONS:The neonatal gut harbors sepsis-causing pathogens, but such organisms are not inevitable members of the normal microbiota. Surveillance microbiology, decolonization, and augmented hygiene might prevent dissemination of invasive bacteria between and within premature infants. 10.1093/cid/ciu084
    Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy-Reply. Achten Niek B,Klingenberg Claus,Plötz Frans B JAMA pediatrics 10.1001/jamapediatrics.2019.6269
    Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy. Zhang Qi,Niu Wenquan JAMA pediatrics 10.1001/jamapediatrics.2019.6260
    Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy. Aghai Zubair H JAMA pediatrics 10.1001/jamapediatrics.2019.6257
    S100A8/A9 is the first predictive marker for neonatal sepsis. Pirr Sabine,Dauter Louise,Vogl Thomas,Ulas Thomas,Bohnhorst Bettina,Roth Johannes,Viemann Dorothee Clinical and translational medicine 10.1002/ctm2.338
    Correction to: miRNA-23b as a biomarker of culture-positive neonatal sepsis. Fatmi Ahlam,Rebiahi Sid Ahmed,Chabni Nafissa,Zerrouki Hanane,Azzaoui Hafsa,Elhabiri Yamina,Benmansour Souheila,Ibáñez-Cabellos José Santiago,Smahi Mohammed Chems-Eddine,Aribi Mourad,García-Giménez José Luis,Pallardó Federico V Molecular medicine (Cambridge, Mass.) 10.1186/s10020-020-00257-0
    Role of C-Reactive Protein for Late-Onset Neonatal Sepsis. Molloy Eleanor J,Strunk Tobias JAMA pediatrics 10.1001/jamapediatrics.2020.2126
    Suspected Materno-Fetal Transmission of Serogroup W Clonal Complex 11 Causing Early-Onset Neonatal Sepsis. Gilbey Timothy,McIver Christopher,Brandenburg Ulrike,Goeman Emma,Polkinghorne Adam,Lahra Monica,Branley James Open forum infectious diseases 10.1093/ofid/ofaa039
    Evaluation of microbiologic and hematologic parameters and E-selectin as early predictors for outcome of neonatal sepsis. Zaki Maysaa el-Sayed,el-Sayed Hesham Archives of pathology & laboratory medicine CONTEXT:Early diagnosis of neonatal sepsis is mandatory. Various markers are used to diagnose the condition. OBJECTIVE:To evaluate the diagnostic value of various clinical data and hematologic parameters, such as total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, and soluble E-selectin (sE-selectin) in identification and outcome of neonatal sepsis. DESIGN:Newborn infants with a clinical diagnosis of sepsis in the neonatal intensive care unit at Mansoura University Children's Hospital during the period between July 2007 and December 2007 were eligible for study. In addition, 30 healthy neonates were included in the study. Complete hematologic and microbiologic laboratory investigations were performed, and serum E-selectin was measured. RESULTS:Plasma sE-selectin levels were significantly higher (P < .001) in infected infants (mean [SD], 156.9 [77.0] ng/mL) than in noninfected (mean [SD], 88.8 [47.1] ng/mL) and healthy infants (mean [SD], 8.67 [3.74] ng/mL). Infants with gram-negative sepsis had higher sE-selectin levels than did those with gram-positive sepsis (P = .04). C-reactive protein was the best laboratory test for diagnosis of neonatal sepsis, with an overall sensitivity and specificity of 86% and 97%, respectively. Performing sE-selectin with C-reactive protein or immature to total ratio tests increased the specificity, but reduced the sensitivity, of the tests for the determination of neonatal sepsis. Plasma sE-selectin levels were higher in nonsurvivors than in survivors (P = .01) and were higher in those with hemodynamic dysfunction than in those without hemodynamic dysfunction (P < .001). CONCLUSIONS:We conclude that plasma sE-selectin levels are elevated in neonatal sepsis. Significant elevation was associated with gram-negative sepsis. Plasma sE-selectin had low diagnostic value when used alone or in combination with other tests; however, it can be used as a prognostic indicator for the outcome of neonatal sepsis. 10.1043/1543-2165-133.8.1291
    Impact of neonatal sepsis calculator in West Midlands (UK). van Hasselt Tim J,McDermott Helen,Surana Pinki,Eltahir Rawia,Macaskill Laura,Jain Raunak,McMullan Nicola,Slee Samantha,Jagga Megha,Naseem Muhammed,Alake Oluwaseyi,Cherry Canada,Miguras Benjamin,Ewer Andrew K, Archives of disease in childhood. Fetal and neonatal edition 10.1136/archdischild-2020-320862
    The Role of Biomarkers in Suspected Neonatal Sepsis. Weitkamp Jörn-Hendrik Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 10.1093/cid/ciaa869
    Genome-wide expression profiles in very low birth weight infants with neonatal sepsis. Cernada María,Serna Eva,Bauerl Christine,Collado María Carmen,Pérez-Martínez Gaspar,Vento Máximo Pediatrics BACKGROUND:Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS:This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays. RESULTS:During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction. CONCLUSIONS:Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings. 10.1542/peds.2013-2552
    Gut microbial colonisation in premature neonates predicts neonatal sepsis. Madan Juliette C,Salari Richard Cowper,Saxena Deepti,Davidson Lisa,O'Toole George A,Moore Jason H,Sogin Mitchell L,Foster James A,Edwards William H,Palumbo Paul,Hibberd Patricia L Archives of disease in childhood. Fetal and neonatal edition BACKGROUND:Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. METHODS:Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. RESULTS:Six neonates were 24-27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. CONCLUSIONS:In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a 'healthy microbiome' present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates. 10.1136/fetalneonatal-2011-301373
    Screening for colonisation with gentamicin-resistant Gram-negative organisms on the neonatal unit: does positive screening predict sepsis? Walker Oliver,Babb Carolyn,Karampatsas Konstantinos,Richards Justin,Kennea Nigel Archives of disease in childhood. Fetal and neonatal edition 10.1136/archdischild-2018-315253
    Epidemiology of infections and antimicrobial use in Greek Neonatal Units. Gkentzi Despoina,Kortsalioudaki Christina,Cailes Benjamin Campbell,Zaoutis Theoklis,Kopsidas John,Tsolia Maria,Spyridis Nikos,Siahanidou Soultana,Sarafidis Kosmas,Heath Paul T,Dimitriou Gabriel, Archives of disease in childhood. Fetal and neonatal edition OBJECTIVE:To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece. DESIGN:Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies. SETTING:16 NNUs in Greece participating in the neonIN infection surveillance network PATIENTS: Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics. RESULTS:459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). (80%) were the most common Gram-positive organisms causing LOS and spp (39%) the most common Gram-negative. Nearly half (45%) of the spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS. CONCLUSIONS:This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required. 10.1136/archdischild-2018-315024
    Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate Outcome in Neonatal Bacterial Sepsis. Harbeson Danny,Francis Freddy,Bao Winnie,Amenyogbe Nelly A,Kollmann Tobias R Frontiers in immunology Bacterial sepsis is one of the leading causes of death in newborns. In the face of growing antibiotic resistance, it is crucial to understand the pathology behind the disease in order to develop effective interventions. Neonatal susceptibility to sepsis can no longer be attributed to simple immune immaturity in the face of mounting evidence that the neonatal immune system is tightly regulated and well controlled. The neonatal immune response is consistent with a "disease tolerance" defense strategy (minimizing harm from immunopathology) whereas adults tend toward a "disease resistance" strategy (minimizing harm from pathogens). One major advantage of disease tolerance is that is less energetically demanding than disease resistance, consistent with the energetic limitations of early life. Immune effector cells enacting disease resistance responses switch to aerobic glycolysis upon TLR stimulation and require steady glycolytic flux to maintain the inflammatory phenotype. Rapid and intense upregulation of glucose uptake by immune cells necessitates an increased reliance on fatty acid metabolism to (a) fuel vital tissue function and (b) produce immunoregulatory intermediates which help control the magnitude of inflammation. Increasing disease resistance requires more energy: while adults have fat and protein stores to catabolize, neonates must reallocate resources away from critical growth and development. This understanding of sepsis pathology helps to explain many of the differences between neonatal and adult immune responses. Taking into account the central role of metabolism in the host response to infection and the severe metabolic demands of early life, it emerges that the striking clinical susceptibility to bacterial infection of the newborn is at its core a problem of metabolism. The evidence supporting this novel hypothesis, which has profound implications for interventions, is presented in this review. 10.3389/fimmu.2018.01918
    PCR for the detection of pathogens in neonatal early onset sepsis. Oeser Clarissa,Pond Marcus,Butcher Philip,Bedford Russell Alison,Henneke Philipp,Laing Ken,Planche Timothy,Heath Paul T,Harris Kathryn PloS one BACKGROUND:A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS:Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS:Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION:Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis. 10.1371/journal.pone.0226817
    Early-onset neonatal sepsis. Simonsen Kari A,Anderson-Berry Ann L,Delair Shirley F,Davies H Dele Clinical microbiology reviews Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. 10.1128/CMR.00031-13
    Enteral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates. Pammi Mohan,Abrams Steven A The Cochrane database of systematic reviews BACKGROUND:Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity despite appropriate antibiotic therapy. Enhancing host defense and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis, NEC, or both, may improve clinical outcomes. OBJECTIVES:The primary objective was to assess safety and efficacy of oral lactoferrin as an adjunct to antibiotics in the treatment of neonates with suspected or confirmed sepsis, NEC, or both. SEARCH METHODS:We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), MEDLINE via PubMed, PREMEDLINE, (1966 to 20 September 2018) Embase (1980 to 20 September 2018), and CINAHL (1982 to 20 September 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retried articles and clinical trials, and the authors' personal files. SELECTION CRITERIA:We included randomized or quasi-randomized controlled trials evaluating enteral lactoferrin (at any dose or duration), used as an adjunct to antibiotic therapy, compared with antibiotic therapy alone (with or without placebo) or other adjuncts to antibiotic therapy to treat neonates at any gestational age up to 44 weeks' postmenstrual age with confirmed or suspected sepsis or necrotizing enterocolitis (Bell's Stage II or III). DATA COLLECTION AND ANALYSIS:We used the standardized methods of Cochrane Neonatal for conducting a systematic review and for assessing the methodological quality of studies (neonatal.cochrane.org/en/index.html). The titles and the abstracts of studies identified by the search strategy were independently assessed by the two review authors and full text versions were obtained for assessment if necessary. Forms were designed to record trial inclusion/exclusion and data extraction. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS:We did not identify any eligible trials evaluating lactoferrin for the treatment of neonatal sepsis or NEC. AUTHORS' CONCLUSIONS:Implications for practice: currently there is no evidence to support or refute the use of enteral lactoferrin, as an adjunct to antibiotic therapy, for the treatment of neonatal sepsis or necrotizing enterocolitis. IMPLICATIONS FOR RESEARCH:given the lack of efficacy of enteral lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis, evaluation of enteral lactoferrin as an adjunctive agent for treatment of sepsis or necrotizing enterocolitis does not appear to be a research priority. 10.1002/14651858.CD007138.pub4
    Dose Rationale for Amoxicillin in Neonatal Sepsis When Referral Is Not Possible. D'Agate Salvatore,Musuamba Flora Tshinanu,Della Pasqua Oscar Frontiers in pharmacology Background:Despite the widespread use of amoxicillin in young children, efforts to establish the feasibility of simplified dosing regimens in resource-limited settings have relied upon empirical evidence of efficacy. Given the antibacterial profile of beta-lactams, understanding of the determinants of pharmacokinetic variability may provide a more robust guidance for the selection of a suitable regimen. Here we propose a simplified dosing regimen based on pharmacokinetic-pharmacodynamic principles, taking into account the impact of growth, renal maturation and disease processes on the systemic exposure to amoxicillin. Materials and Methods:A meta-analytical modeling approach was applied to allow the adaptation of an existing pharmacokinetic model for amoxicillin in critically ill adults. Model parameterization was based on allometric concepts, including a maturation function. Clinical trial simulations were then performed to characterize exposure, as defined by secondary pharmacokinetic parameters (AUC, C, C) and T>MIC. The maximization of the T>MIC was used as criterion for the purpose of this analysis and results compared to current WHO guidelines. Results:A two-compartment model with first order absorption and elimination was found to best describe the pharmacokinetics of amoxicillin in the target population. In addition to the changes in clearance and volume distribution associated with demographic covariates, our results show that sepsis alters drug distribution, leading to lower amoxicillin levels and longer half-life as compared to non-systemic disease conditions. In contrast to the current WHO guidelines, our analysis reveals that amoxicillin can be used as a fixed dose regimen including two weight bands: 125 mg b.i.d. for patients with body weight < 4.0 kg and 250 mg b.i.d. for patients with body weight ≥ 4.0 kg. Conclusions:In addition to the effect of developmental growth and renal maturation, sepsis also alters drug disposition. The use of a model-based approach enabled the integration of these factors when defining the dose rationale for amoxicillin. A simplified weight-banded dosing regimen should be considered for neonates and young infants with sepsis when referral is not possible. 10.3389/fphar.2020.521933
    Poor postnatal weight growth is a late finding after sepsis in very preterm infants. Flannery Dustin D,Jensen Erik A,Tomlinson Lauren A,Yu Yinxi,Ying Gui-Shuang,Binenbaum Gil, Archives of disease in childhood. Fetal and neonatal edition OBJECTIVE:To characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth. DESIGN:Retrospective matched cohort study using data from the Postnatal Growth and Retinopathy of Prematurity study. Participants were born with birth weights of <1500 g or gestational ages of <32 weeks between 2006 and 2011 at 29 neonatal centres in the USA and Canada. Sepsis was defined as a culture-confirmed bacterial or fungal infection of the blood or cerebrospinal fluid before 36 weeks' postmenstrual age (PMA). Growth was assessed as the change in weight z-score between birth and 36 weeks' PMA. RESULTS:Of 4785 eligible infants, 813 (17%) developed sepsis and 693 (85%) were matched 1:1 to controls. Sepsis was associated with a greater decline in weight z-score (mean difference -0.09, 95% CI -0.14 to -0.03). Postnatal weight growth failure (decline in weight z- score>1) was present in 237 (34%) infants with sepsis and 179 (26%) controls (adjusted OR 1.49, 95% CI 1.12 to 1.97). Longitudinal growth trajectories showed similar initial changes in weight z-scores between infants with and without sepsis. By 3 weeks after sepsis onset, there was a greater decline in weight z-scores relative to birth values in those with sepsis than without sepsis (delta z-score -0.89 vs -0.77; mean difference -0.12, 95% CI -0.18 to -0.05). This significant difference persisted until 36 weeks or discharge. CONCLUSION:Infants with sepsis had similar early weight growth trajectories as infants without sepsis but developed significant deficits in weight that were not apparent until several weeks after the onset of sepsis. 10.1136/archdischild-2020-320221
    Rapid detection of bacteria in bloodstream infections using a molecular method: a pilot study with a neonatal diagnostic kit. Mazzucchelli Iolanda,Garofoli Francesca,Angelini Micol,Tinelli Carmine,Tzialla Chryssoula,Decembrino Lidia Molecular biology reports Neonatal sepsis is a life-threatening condition and its early diagnosis is crucial for infant survival. Identifying responsible pathogens is a key step. Blood culture (BC) is the gold standard, but more rapid and specific diagnostic methods are needed. We evaluated the reliability and utility of 3 h turnaround time diagnostic molecular kit, "EuSepScreen lattanti "CE IVD marked, (EuSepScreen lattanti, Eurospital Spa Trieste, Italy) specifically targeted to detect 4 pathogens in neonatal sepsis: Klebsiella pneumoniae (KP), Escherichia coli (EC), Streptococcus agalactiae (GBS), and Lysteria monocytogenes. We evaluated 69 neonates, 40 full term and 29 preterm infants, with suspected bloodstream infection, who, overall the routine clinical procedures, were tested using the molecular kit. Kit results were compared to BC outcomes. Nineteen cases for early onset sepsis (EOS) were evaluated, 2 of them resulted positive to a molecular kit and to BC (both for GBS and EC). In the 50 cases of suspected late onset sepsis (LOS), 7 infants reported positive and coincident results to both the methods, in 3 further cases the molecular kit identified pathogens (EC) in neonates with negative BC result; in 10 cases BC revealed etiological pathogens exceeding the molecular kit possibility of identification. In case of EOS, results of the molecular kit were coincident to these of BC, but available in 3 h turnaround time, which is an advantage, so the kit may actually be an "add-on tool" for EOS, with reference to EC and GBS, but a larger study with a greater number of EOS cases are needed to validate its usefulness in the NICU. Regarding LOS the restricted panel of identifiable microorganisms failed to provide timely information for sepsis diagnosis, highlighting the need of enlarged number microorganisms for the diagnosis of LOS.Trial registration number: NCT03884894. 10.1007/s11033-019-05138-2
    The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Ng Pak Cheung,Ma Terence Ping Yuen,Lam Hugh Simon Archives of disease in childhood. Fetal and neonatal edition Biomarkers have been used to differentiate systemic neonatal infection and necrotising enterocolitis (NEC) from other non-infective neonatal conditions that share similar clinical features. With increasing understanding in biochemical characteristics of different categories of biomarkers, a specific mediator or a panel of mediators have been used in different aspects of clinical management in neonatal sepsis/NEC. This review focuses on how these biomarkers can be used in real-life clinical settings for daily surveillance, bedside point-of-care testing, early diagnosis and predicting the severity and prognosis of neonatal sepsis/NEC. In addition, with recent development of 'multi-omic' approaches and rapid advancement in knowledge of bioinformatics, more novel biomarkers and unique signatures of mediators would be discovered for diagnosis of specific diseases and organ injuries. 10.1136/archdischild-2014-307656
    Clinical trials in neonatal sepsis. Oeser Clarissa,Lutsar Irja,Metsvaht Tuuli,Turner Mark A,Heath Paul T,Sharland Mike The Journal of antimicrobial chemotherapy Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy. 10.1093/jac/dkt297
    Diagnostic Value of Neutrophil to Lymphocyte Ratio and Mean Platelet Volume on Early Onset Neonatal Sepsis on Term Neonate. Karabulut Birol,Alatas Silem Ozdem Journal of pediatric intensive care By setting out from increased neutrophil count, decreased lymphocyte count, and increased mean platelet volume (MPV), which is a result of the effect of inflammation on blood cells, we aimed to investigate whether neutrophil to lymphocyte ratio (NLP) and MPV can be used as an auxiliary parameter for the diagnosis of early-onset neonatal sepsis (EOS). This study was conducted by analyzing term neonates with EOS and physiological jaundice who were admitted to the neonatal intensive care unit of Izmir Katip Celebi University Ataturk Training and Research Hospital. A total of 63 neonate files were examined to include 30 term neonates with EOS, and 77 neonate files were examined to include 30 term neonates with physiological jaundice as a control group. NLR had an area under the curve (AUC) of 0.891 for prediction of EOS. At a cut-off level of 1.42, NLR had a likelihood ratio (LR) of 5.5, sensitivity of 88%, a specificity of 84%, a positive predictive value (PPV) of 84.6%, and a negative predictive value (NPV) of 87.5%. MPV had an AUC of 0.666 for the prediction of EOS and at a cut-off level of 9.3 fL, MPV had an LR of 1.23, sensitivity of 84%, a specificity of 32%, a PPV of 55.2%, and an NPV of 66.6%. In conclusion, this study provides evidence that NLR and MPV can be used in addition to conventional parameters in the diagnosis of EOS. 10.1055/s-0040-1715104
    High serum trypsin levels and the -409 T/T genotype of PRSS1 gene are susceptible to neonatal sepsis. Chen Qingquan,Xue Heng,Chen Min,Gao Feng,Xu Jianping,Liu Qicai,Yang Xiulin,Zheng Lie,Chen Hong Inflammation Neonatal sepsis remains an important and common cause of morbidity and mortality among newborn infants, especially in developing countries. The aim of the present study was to determine whether serum trypsin levels and genotypes of cationic trypsinogen (PRSS1) gene could be served as markers for predicting neonatal sepsis. The serum trypsin levels and genotypes of PRSS1 were examined in both 50 infants with infection during neonatal period and 56 healthy neonates as controls. The infected infants were further subdivided into infants with sepsis group (n=18) and infected infants without sepsis (n=32). The genotype of PRSS1 was analyzed by direct sequencing, and the serum trypsin level was measured by immunoassay. It showed that the median value of serum trypsin was significantly higher in infected infants (31.90 ng/mL) than in controls (12.85 ng/mL; P=0.030). More importantly, sepsis subgroup (50.95 ng/mL) had significantly higher median serum trypsin than infected infants without sepsis subgroup (19.10 ng/mL) and controls (12.85 ng/mL) (P=0.015 and P=0.002, respectively). Additionally, the median serum trypsin levels were found significantly higher in infants who had T/T (37.90 ng/mL) genotype of PRSS1 compared with those who had C/T genotype (12.80 ng/mL; P=0.005). This study suggested that serum trypsin and rs10273639 C/T of PRSS1 were revealed to be novel markers for predicting neonatal sepsis. 10.1007/s10753-014-9904-3
    The Problem of Microbial Dark Matter in Neonatal Sepsis. Sinnar Shamim A,Schiff Steven J Emerging infectious diseases Neonatal sepsis (NS) kills 750,000 infants every year. Effectively treating NS requires timely diagnosis and antimicrobial therapy matched to the causative pathogens, but most blood cultures for suspected NS do not recover a causative pathogen. We refer to these suspected but unidentified pathogens as microbial dark matter. Given these low culture recovery rates, many non-culture-based technologies are being explored to diagnose NS, including PCR, 16S amplicon sequencing, and whole metagenomic sequencing. However, few of these newer technologies are scalable or sustainable globally. To reduce worldwide deaths from NS, one possibility may be performing population-wide pathogen discovery. Because pathogen transmission patterns can vary across space and time, computational models can be built to predict the pathogens responsible for NS by region and season. This approach could help to optimally treat patients, decreasing deaths from NS and increasing antimicrobial stewardship until effective diagnostics that are scalable become available globally. 10.3201/eid2611.200004
    Soluble CD14 subtype (sCD14-ST) as biomarker in neonatal early-onset sepsis and late-onset sepsis: a systematic review and meta-analysis. van Maldeghem Iris,Nusman Charlotte M,Visser Douwe H BMC immunology BACKGROUND:Early diagnosis of bacterial sepsis in neonates is hampered by non-specific symptoms and the lack of rapid responding laboratory measures. The biomarker soluble CD14 subtype (sCD14-ST) seems promising in the diagnostic process of neonatal sepsis. In order to evaluate the differences in diagnostic accuracy of sCD14-ST between early onset sepsis (EOS) and late onset sepsis (LOS) we assessed this systematic review and meta-analysis. RESULTS:Twelve articles were included in the systematic review and 10 in the meta-analysis. There was a high risk of bias on patient selection, index test and/or flow and timing. The overall quality of the included studies was moderate. At sepsis onset a consequently higher level of sCD14-ST was found in septic neonates compared to healthy controls with significant higher levels in LOS compared to EOS. In the first 24 h after sepsis onset a significant increase in pooled means of plasma sCD14-ST levels was seen in EOS (t(71.6) = 7.3, p < .0001) while this was not seen in LOS or healthy controls. Optimal cut-off values ranged from 305 to 672 ng/l for EOS cases versus healthy controls. The pooled sensitivity was 81% (95%CI: 0.76-0.85), the pooled specificity was 86% (0.81-0.89) with an AUC of 0.9412 (SE 0.1178). In LOS optimal cut-off values ranged from 801 to 885 ng/l with a pooled sensitivity of 81% (0.74-0.86) and a pooled specificity of 100% (0.98-1.00). An AUC and SROC was not estimable in LOS because of the low number of studies. CONCLUSIONS:sCD14-ST is a promising and rapid-responding diagnostic biomarker for EOS and LOS. The difference in pooled means between EOS and LOS underlines the importance to consider EOS and LOS as two different disease entities, requiring separate analysis in original articles and systematic reviews. 10.1186/s12865-019-0298-8
    Inflammatory mediators of systemic inflammation in neonatal sepsis. Sugitharini V,Prema A,Berla Thangam E Inflammation research : official journal of the European Histamine Research Society ... [et al.] OBJECTIVE AND DESIGN:Sepsis refers to severe systemic inflammation in response to invading pathogens. To understand the molecular events that initiate the systemic inflammatory response, various inflammatory mediators were analyzed in neonatal sepsis samples and compared with normal samples. MATERIALS AND METHODS:We initially measured the levels of the various classical inflammatory mediators such as acute phase proteins [C-reactive protein (CRP) and procalcitonin (PCT)], granule-associated mediators (NE, MPO and NO), proinflammatory cytokines [tumour necrosis factor-α (TNFα), IL-1β and IL-6), antiinflammatory cytokines (IL-10 and IL-13) and chemokines [IL-8 and monocyte chemotactic protein (MCP-1)] and novel cytokines (IL-12/IL-23p40, IL-21 and IL-23) using ELISA. We also used the human inflammation antibody array membrane to profile the inflammatory proteins that are involved in neonatal sepsis. RESULTS:There were significantly higher levels of CRP (5.4 ± 0.70 mg/L), PCT (1.500 ± 0.2400 μg/L); NE (499.2 ± 22.01 μg/L), NO (54.22 ± 3.131 μM/L); TNFα (396.6 ± 37.40 pg/mL), IL-1β (445.3 ± 34.25 pg/mL), IL-6 (320.9 ± 43.38 pg/mL); IL-8 (429.5 ± 64.08 pg/mL) MCP-1 (626.25 ± 88.91 pg/mL), IL-10 (81.80 ± 9.45 pg/mL), IL-12/IL-23p40 (30.25 ± 0.6 pg/mL), IL-21 (8,263.3 ± 526.8 pg/mL) and IL-23 (6,083 ± 781.3 pg/mL) in neonates with sepsis compared to normal. The levels of MPO (21.20 ± 3.099 ng/mL) were downregulated, whereas there was no change in IL-13 (188.7 ± 10.63 pg/mL) levels in septic neonates when compared with normal. Using the human inflammation antibody array membrane, we detected the presence of 17 inflammatory proteins such as IL-3, IL6R, IL12p40, IL-16, TNFα, TNFβ, TNF R1, chemokines I-309, IP-10 (IFN-γ inducible protein 10), MCP-1, MCP-2, MIP 1β (macrophage inflammatory protein), MIP-1δ, eotaxin-2, growth factors TGFβ1 (transforming growth factor beta), PDGF (platelet derived growth factor), and cell adhesion molecule ICAM-1 (intracellular adhesion molecule) that were upregulated whereas RANTES which was downregulated in neonatal sepsis. CONCLUSION:The simultaneous secretion and release of multiple mediators such as proinflammatory cytokines and chemokines, cell adhesion molecules, and growth factors were found to be involved in the initiation of systemic inflammation in neonatal sepsis. Therefore, measuring the concentration of multiple mediators may help in the early detection of neonatal sepsis and help to avoid unnecessary antibiotic treatment. 10.1007/s00011-013-0661-9
    Neonatal sepsis: an old problem with new insights. Shah Birju A,Padbury James F Virulence Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW<1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. 10.4161/viru.26906
    Tackling antimicrobial resistance in neonatal sepsis. Folgori Laura,Ellis Sally J,Bielicki Julia A,Heath Paul T,Sharland Mike,Balasegaram Manica The Lancet. Global health 10.1016/S2214-109X(17)30362-5
    TLR2-induced IL-10 production impairs neutrophil recruitment to infected tissues during neonatal bacterial sepsis. Andrade Elva B,Alves Joana,Madureira Pedro,Oliveira Liliana,Ribeiro Adília,Cordeiro-da-Silva Anabela,Correia-Neves Margarida,Trieu-Cuot Patrick,Ferreira Paula Journal of immunology (Baltimore, Md. : 1950) Sepsis is the third most common cause of neonatal death, with Group B Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of neonatal septicemia is still unsolved. We described previously that host susceptibility to GBS infection is due to early IL-10 production. In this study, we investigated whether triggering TLR2 to produce IL-10 is a risk factor for neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups, neonatal TLR2-deficient mice were resistant to GBS-induced sepsis. Moreover, if IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This increased survival rate was due to an efficient recruitment of neutrophils to infected tissues that leads to bacterial clearance, thus preventing the development of sepsis. To confirm that IL-10 produced through TLR2 activation prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB4. Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with Pam3CSK4. However, the migration was restored in Pam3CSK4-treated pups when IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice). Our findings highlight that TLR2-induced IL-10 production is a key event in neonatal susceptibility to bacterial sepsis. 10.4049/jimmunol.1301752
    Beyond sepsis: Staphylococcus epidermidis is an underestimated but significant contributor to neonatal morbidity. Dong Ying,Speer Christian P,Glaser Kirsten Virulence Staphylococcus epidermidis accounts for the majority of cases of neonatal sepsis. Moreover, it has been demonstrated to be associated with neonatal morbidities, such as bronchopulmonary dysplasia (BPD), white matter injury (WMI), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP), which affect short-term and long-term neonatal outcome. Imbalanced inflammation has been considered to be a major underlying mechanism of each entity. Conventionally regarded as a harmless commensal on human skin, S. epidermidis has received less attention than its more virulent relative Staphylococcus aureus. Particularities of neonatal innate immunity and nosocomial environmental factors, however, may contribute to the emergence of S. epidermidis as a significant nosocomial pathogen. Neonatal host response to S. epidermidis sepsis has not been fully elucidated. Evidence is emerging regarding the implication of S. epidermidis sepsis in the pathogenesis of neonatal inflammatory diseases. This review focuses on the interplay among S. epidermidis, neonatal innate immunity and inflammation-driven organ injury. 10.1080/21505594.2017.1419117
    Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis. Wagstaff Jadon S,Durrant Robert J,Newman Michael G,Eason Rachael,Ward Robert M,Sherwin Catherine M T,Enioutina Elena Y Frontiers in pharmacology Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (>3 and ≤28 days of birth, LOS) and categorized as culture-confirmed sepsis if a pathogen was cultured from the blood and unconfirmed if all blood cultures were negative with no potentially contaminated blood cultures. Of 1,010 neonates in the EOS cohort, 23 (2.3%) were culture-confirmed, most with (42%). Treatment for unconfirmed EOS lasted an average of 6.1 days with primarily gentamicin and ampicillin while confirmed patients were treated for an average of 12.3 days with increased administration of cefotaxime. Of 311 neonates in the LOS cohort, 62 (20%) were culture-confirmed, most culturing coagulase negative staphylococci (46%). Treatment courses for unconfirmed LOS lasted an average of 7.8 days while confirmed patients were treated for an average of 11.4 days, these patients were primarily treated with vancomycin and gentamicin. The use of cefotaxime for unconfirmed EOS and LOS increased throughout the study period. Cefotaxime administration was associated with an increase in neonatal mortality, even when potential confounding factors were added to the logistic regression model (adjusted odds ratio 2.8, 95%CI [1.21, 6.88], p = 0.02). These results may not be generalized to all hospitals and the use of cefotaxime may be a surrogate for other factors. Given the low rate of blood culture positive diagnosis and the high exposure rate of empiric antibiotics, this patient population might benefit from improved diagnostics with reevaluation of antibiotic use guidelines. 10.3389/fphar.2019.01191
    Up-regulation of BTLA expression in myeloid dendritic cells associated with the treatment outcome of neonatal sepsis. Wang Wan-Dang,Yang Xu-Ran,Guo Ming-Fa,Pan Zhi-Feng,Shang Mei,Qiu Ming-Jin,Wu Jing-Yi,Jia Jing,Liang Ying-Liang,Zheng Wen-Ting,Xu Jun-Fa,Chen Guang-Hui Molecular immunology Dentritic cells (DCs) dysfunction has been verified detrimental for sepsis and B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to be associated with DCs dysfunction. However, the role of BTLA expression in myeloid DCs (mDCs) in neonatal sepsis is unknown. In the current study, we found BTLA-expressing mDCs were elevated in neonates with sepsis and the BTLA expression level in mDCs was positively correlated to the severity of sepsis. The presence of BTLA negatively regulated the phagocytosis capacity and bactericidal ability of mDCs as well as the maturation markers expression of mDCs. Our data also showed BTLAmDCs shifted into an anti-inflammatory phenotype with decreased expression of IL-6, TNF-α and IL-12, but increased IL-10. in addition, we found BTLA expression indeedly altered the mDCs allo-stimulatory capacity. Therefore, BTLA expression in mDCs could be a useful predictive marker for neonatal sepsis and targeting BTLA expression in mDCs may be a new therapeutic strategy. 10.1016/j.molimm.2021.03.007
    Evaluation of a turbidimetric C-reactive protein assay to monitor early-onset neonatal sepsis in South Kivu (Democratic Republic of the Congo). Mulinganya Guy,Balolebwami Serge,Zigabe Serge,Mongane Jules,Nianci Isia,Burume Adrien,Hendwa Erick,Kampara Freddy,Maheshe Ghislain,Sadiki Kishabongo Antoine,Bisimwa Ghislain,Cools Piet,Speeckaert Marijn,Callens Steven,Delanghe Joris Clinical chemistry and laboratory medicine OBJECTIVES:Neonatal sepsis, a condition defined as bacteremia within the first month of life accompanied by signs of systemic infection, is the most preventable cause of infant mortality in sub-Saharan Africa. Despite the development of new infection markers, C-reactive protein (CRP) is the most extensively studied acute phase reactant so far and the preferred index in many neonatal intensive care units (NICUs). The aim of the present study was to evaluate an affordable, non-commercial turbidimetric CRP assay for monitoring early-onset neonatal sepsis (EOS). METHODS:A total of 148 neonates admitted at the NICU of the Hôpital Provincial Général de Référence de Bukavu to diagnose and to monitor EOS were enrolled in the study. CRP was assayed using a functional turbidimetric assay based on the interaction of CRP with phosphocholine containing particles (Intralipid). RESULTS:In total, 62/148 (41.9%) cases were identified as blood culture-proven EOS. Different serum CRP slopes were observed among the different birth weight categories. Moreover, the serum (CRP 48 h-CRP 12 h) difference and the birth weight predicted the outcome of these septic newborns. CONCLUSIONS:Our turbidimetric CRP assay is a potential novel tool that can be used in the management of EOS in sub-Saharan Africa. The simplicity of the assay and the extremely low price make the CRP method very well suited for developing countries. 10.1515/cclm-2020-0309
    Simplified antibiotic regimens for community management of neonatal sepsis. Nair Harish The Lancet. Global health 10.1016/S2214-109X(16)30358-8
    Does bovine lactoferrin prevent late-onset neonatal sepsis? Doyle Lex W,Cheong Jeanie L Y Lancet (London, England) 10.1016/S0140-6736(18)32390-0
    Early-Onset Neonatal Sepsis: A Continuing Problem in Need of Novel Prevention Strategies. Stoll Barbara J Pediatrics 10.1542/peds.2016-3038
    miRNA-23b as a biomarker of culture-positive neonatal sepsis. Fatmi Ahlam,Rebiahi Sid Ahmed,Chabni Nafissa,Zerrouki Hanane,Azzaoui Hafsa,Elhabiri Yamina,Benmansour Souheila,Ibáñez-Cabellos José Santiago,Smahi Mohammed Chems-Eddine,Aribi Mourad,García-Giménez José Luis,Pallardó Federico V Molecular medicine (Cambridge, Mass.) BACKGROUND:Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. METHODS:Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1-2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. RESULTS:miR-23b levels increased in premature and full-term newborns in early onset sepsis (p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates (p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls (p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types (p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = - 0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. CONCLUSIONS:Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring. 10.1186/s10020-020-00217-8
    Preterm premature rupture of membranes and the rate of neonatal sepsis after two courses of antenatal corticosteroids. Gyamfi-Bannerman Cynthia,Son Moeun Obstetrics and gynecology OBJECTIVE:To evaluate whether a second antenatal corticosteroid course is associated with an increased risk of neonatal sepsis after preterm premature rupture of membranes (PROM). METHODS:This secondary analysis is a cohort study with data from the Maternal-Fetal Medicine Units study on magnesium for neuroprotection. Women with singleton gestations and preterm PROM were eligible. The primary exposure was one compared with two antenatal corticosteroid courses. The primary outcome, neonatal sepsis, was compared between exposed groups. Patient characteristics were analyzed by χ2 for categorical variables and Student t test or Wilcoxon rank-sum for continuous variables where appropriate. Predictors of neonatal sepsis were analyzed by multivariable logistic regression. RESULTS:One thousand six hundred forty-one patients were eligible. Neonatal sepsis was similar among neonates born to mothers who received one or two antenatal corticosteroid courses (16.2% compared with 17.2%, P=.756, respectively). Adjusting for confounders, the factors associated with neonatal sepsis were length of time from membrane rupture to delivery (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.02-2.26), respiratory distress syndrome (OR 2.11, 95% CI 1.45-3.07), gestational age at delivery in days (OR 0.98, 95% CI 0.95-0.99) and birth weight per 100 g (OR 0.85, 95% CI 0.77-0.94). CONCLUSION:A second maternal antenatal corticosteroid course was not associated with an increased rate neonatal sepsis. 10.1097/AOG.0000000000000460
    Association of Neutrophil-Lymphocyte Ratio and the Presence of Neonatal Sepsis. Li Tiewei,Dong Geng,Zhang Min,Xu Zhe,Hu Yidi,Xie Bo,Wang Yuewu,Xu Bangli Journal of immunology research The neutrophil-lymphocyte ratio (NLR) is an emerging risk factor of sepsis that is receiving increasing attention. However, the relationship between NLR and the presence of sepsis in neonates is poorly studied. Here, we retrospectively recruited 1480 neonates and collected and analyzed relevant clinical and laboratory data. According to the International Pediatric Sepsis Consensus, 737 neonates were diagnosed with sepsis, and 555 neonates were suspected for having infection. Neonates with hyperbilirubinemia ( = 188) served as controls. Neonates with sepsis had significantly elevated neutrophil counts and NLR ( < 0.001). The proportion of neonates with sepsis increased significantly from 41.6% when NLR < 0.91 to 66.2% when NLR > 1.88 group ( < 0.001). Multiple logistic regression analysis showed that NLR was an independent risk factor for the presence of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value NLR for predicting the presence of neonatal sepsis was 1.62 (area under curve (AUC) = 0.63, 95% CI 0.60-0.66, < 0.001). In conclusion, our data suggest that elevated NLR levels are associated with a higher neonatal sepsis risk. 10.1155/2020/7650713
    Is lactoferrin still a treatment option to reduce neonatal sepsis? Ochoa Theresa J The Lancet. Child & adolescent health 10.1016/S2352-4642(20)30137-1
    Comparison of the management recommendations of the Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC) with NICE guideline CG149 in infants ≥34 weeks' gestation who developed early-onset sepsis. Morris Rachel,Jones Steve,Banerjee Sujoy,Collinson Andrew,Hagan Hannah,Walsh Hannah,Thornton Graham,Barnard Ian,Warren Chris,Reid Jennifer,Busfield Alison,Matthes Jean Archives of disease in childhood. Fetal and neonatal edition OBJECTIVE:To compare the management recommendations of the Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC) with National Institute for Health and Care Excellence (NICE) guideline CG149 in infants ≥34 weeks' gestation who developed early-onset sepsis (EOS). DESIGN:Retrospective multicentre study. SETTING:Five maternity services in South West of England and Wales. PATIENTS:70 infants with EOS (<72 hours) confirmed on blood or cerebrospinal fluid culture. METHODS:Retrospective virtual application of NICE and SRC through review of maternal and neonatal notes. MAIN OUTCOME MEASURE:The number of infants recommended antibiotics by 4 hours of birth. RESULTS:The incidence of EOS ≥34 weeks was 0.5/1000 live births. Within 4 hours of birth, antibiotics were recommended for 39 infants (55.7%) with NICE, compared with 27 (38.6%) with SRC. The 12 infants advised early treatment by NICE but not SRC remained well, only one showing transient mild symptoms after 4 hours. Another four babies received antibiotics by 4 hours outside NICE and SRC guidance. The remaining 27 infants (38.6%) received antibiotics when symptomatic after 4 hours. Only one infant who was unwell from birth, died. Eighty-one per cent of all EOS infants were treated for clinical reasons rather than for risk factors alone. CONCLUSION:While both tools were poor in identifying EOS within 4 hours, NICE was superior to SRC in identifying asymptomatic cases. Currently, four out of five EOS have symptoms at first identification, the majority of whom present within 24 hours of birth. Antibiotic stewardship programmes using SRC should include enhanced observation for infants currently treated within NICE guidance. 10.1136/archdischild-2019-317165
    Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis. Yang Ai-Ping,Liu Jun,Yue Lei-He,Wang Hong-Qi,Yang Wen-Juan,Yang Guo-Hui Clinical chemistry and laboratory medicine BACKGROUND:The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis. METHODS:The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis. RESULTS:Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers. CONCLUSIONS:nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers. 10.1515/cclm-2015-0277
    The Diagnostic Performance of Interleukin-6 and C-Reactive Protein for Early Identification of Neonatal Sepsis. Tessema Belay,Lippmann Norman,Willenberg Anja,Knüpfer Matthias,Sack Ulrich,König Brigitte Diagnostics (Basel, Switzerland) Interleukin-6 (IL-6) and C-reactive protein (CRP) are being used for diagnosis of sepsis. However, studies have reported varying cut-off levels and diagnostic performance. This study aims to investigate the optimal cut-off levels and performance of IL-6 and CRP for the diagnosis of neonatal sepsis. The study was conducted at the University Hospital of Leipzig, Germany from November 2012 to June 2020. A total of 899 neonates: 104 culture proven sepsis, 160 clinical sepsis, and 625 controls were included. Blood culture was performed using BacT/ALERT 3D system. IL-6 and CRP were analyzed by electrochemiluminescent immunoassay and immunoturbidimetric assay, respectively. Data were analyzed using SPSS 20 statistical software. Among neonates with proven sepsis, the optimal cut-off value of IL-6 was 313.5 pg/mL. The optimal cut-off values for CRP in 5 days serial measurements (CRP1, CRP2, CRP3, CRP4, and CRP5) were 2.15 mg/L, 8.01 mg/L, 6.80 mg/L, 5.25 mg/L, and 3.72 mg/L, respectively. IL-6 showed 73.1% sensitivity, 80.2% specificity, 37.6% PPV, and 94.8% NPV. The highest performance of CRP was observed in the second day with 89.4% sensitivity, 97.3% specificity, 94.5% PPV, and 98.3% NPV. The combination of IL-6 and CRP showed increase in sensitivity with decrease in specificity. In conclusion, this study defines the optimal cut-off values for IL-6 and CRP. The combination of IL-6 and CRP demonstrated increased sensitivity. The CRP 2 at cut-off 8.01 mg/L showed the highest diagnostic performance for identification of culture negative clinical sepsis cases. We recommend the combination of IL-6 (≥313.5 pg/mL) and CRP1 (≥2.15 mg/L) or IL-6 (≥313.5 pg/mL) and CRP2 (≥8.01 mg/L) for early and accurate diagnosis of neonatal sepsis. The recommendation is based on increased sensitivity, that is, to minimize the risk of any missing cases of sepsis. The CRP2 alone at cut-off 8.01 mg/L might be used to identify clinical sepsis cases among culture negative sepsis suspected neonates in hospital settings. 10.3390/diagnostics10110978
    Evaluation of Procalcitonin, C-Reactive Protein, and Interleukin-6 as Early Markers for Diagnosis of Neonatal Sepsis. Morad Emad A,Rabie Rehab A,Almalky Mohamed A,Gebriel Manar G International journal of microbiology Background:Neonatal sepsis diagnosis is a challenge because of its nonspecific presentation together with low sensitivity of the time-consuming bacterial cultures. So, many sepsis markers, like C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6), are emerging to improve its diagnosis. Aim:This study was done to investigate the role of CRP, PCT, and IL-6 in promoting the early diagnosis of neonatal sepsis in an attempt to decrease morbidity and mortality. Methods:This cross-sectional study was conducted on 50 neonates suspected with sepsis enrolled from the neonatal intensive care unit (NICU) of Zagazig University Hospitals, Egypt. Blood cultures for these neonates were done before starting antibiotics. Also, bacterial DNA was revealed from the blood by broad-range 16S rDNA polymerase chain reaction (PCR). Measurements of CRP using the immunoturbidimetry method, PCT using fluorescence immunoassay quantitative method, and IL-6 using commercially available ELISA kit were done to all enrolled neonates. Results:Forty-one neonates with proved sepsis were found to be positive in blood culture and/or PCR for bacterial 16S rDNA. The most common isolated organisms were (61.3%), followed by (9.7%) and (9.7%). We detected much significant higher levels of PCT, CRP, and IL-6 in the proved sepsis group than the suspected neonatal sepsis cases ( ≤ 0.001, 0.001, and 0.004, respectively). Serum PCT levels showed the highest sensitivity, specificity, PPV, NPV, and accuracy of 97.6%, 89%, 97%, 88.9%, and 96% than other studied sepsis markers. Conclusion:PCT has satisfactory characteristics as a good marker than IL-6 and CRP for the diagnosis of neonatal sepsis. 10.1155/2020/8889086
    Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes. Chiossi Giuseppe,Di Tommaso Mariarosaria,Monari Francesca,Consonni Sara,Strambi Noemi,Zoccoli Sofia Gambigliani,Seravalli Viola,Comerio Chiara,Betti Marta,Cappello Anna,Vergani Patrizia,Facchinetti Fabio,Locatelli Anna European journal of obstetrics, gynecology, and reproductive biology OBJECTIVE:Expectant management in patients with prelabor preterm rupture of membranes between between 34 and 36 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN:retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS:258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34 and 34 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM. 10.1016/j.ejogrb.2021.03.036
    The Spartacus Problem: Diagnostic Inefficiency of Neonatal Sepsis. Cantey Joseph B Pediatrics 10.1542/peds.2019-2576
    Platelet indices as a predictive marker in neonatal sepsis and respiratory distress in preterm prelabor rupture of membranes. Mishra Sanjay,Jaiswar Shyampyari,Saad Sumaiya,Tripathi Shalini,Singh Nisha,Deo Sujata,Agarwal Monika,Mishra Neetu International journal of hematology Preterm Prelabor rupture of membranes (PPROM) accompanies 2-3% of all pregnancies and 1/3rd of all preterm deliveries leading to intraamniotic infection, postpartum infections, sepsis along with perinatal morbidity and mortality worldwide. Early diagnosis and treatment can prevent the complications of PPROM and improve mother and child health. The platelet indices (platelet count, Mean platelet volume, Plateletcrit and Immature platelet fraction) could be a useful predictive parameters in PPROM, as platelets are acute phase reactants and there parameters may vary with inflammation and increased platelet consumption/production. In the present study, Mean Platelet volume (MPV) levels showed significant increase in cases as compared to controls (10.47 ± 1.92 fl Vs 8.84 ± 1.30 fl; P < 0.004). Plateletcrit (PCT) levels were also significantly increased in cases with respect to controls (0.22 ± 0.10% Vs 0.18 ± 0.05%; P = 0.004). Immature platelet fraction (IPF) is significantly increased in cases than in control subjects (8.73 ± 6.67% Vs 4.43 ± 1.75%; P < 0.001). Also, Mean Platelet volume (MPV) levels were found to be significantly higher in subjects whose neonate had developed sepsis(11.39 ± 1.69 fl Vs 8.91 ± 1.31 fl; P < 0.001) and respiratory distress (10.62 ± 2.09 fl Vs 9.26 ± 1.56 fl; P = 0.003). Similarly, PCT was significantly higher in groups with positive neonatal sepsis (0.32 ± 0.74% Vs 0.19 ± 0.65%; P = 0.010) and with respiratory distress (0.24 ± 0.78% Vs 0.18 ± 0.59%; P < 0.001). Levels of IPF were also increased in positive neonatal sepsis group (10.11 ± 6.27% Vs 5.06 ± 4.07%; P < 0.001) and respiratory distress group (9.11 ± 6.38% Vs 5.54 ± 4.43%; P = 0.009). The findings suggest that maternal platelet parameters (MPV, PCT and IPF) can be utilized as evidence of early predictors of development of neonatal sepsis and respiratory distress and may be considered as a predictive markers for adverse neonatal outcome. 10.1007/s12185-020-03025-2
    C-Reactive Protein Testing in Late-Onset Neonatal Sepsis: Hazardous Waste. Cantey Joseph B,Bultmann Charlene R JAMA pediatrics 10.1001/jamapediatrics.2019.5684
    The Holy Grail of Ascertainment of Early-Onset Neonatal Sepsis. Benitz William E,Long Sarah S The Journal of pediatrics 10.1016/j.jpeds.2019.05.072
    Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014. Schrag Stephanie J,Farley Monica M,Petit Susan,Reingold Arthur,Weston Emily J,Pondo Tracy,Hudson Jain Jennifer,Lynfield Ruth Pediatrics BACKGROUND:Group B Streptococcus (GBS) and Escherichia coli have historically dominated as causes of early-onset neonatal sepsis. Widespread use of intrapartum prophylaxis for GBS disease led to concerns about the potential adverse impact on E coli incidence. METHODS:Active, laboratory, and population-based surveillance for culture-positive (blood or cerebrospinal fluid) bacterial infections among infants 0 to 2 days of age was conducted statewide in Minnesota and Connecticut and in selected counties of California and Georgia during 2005 to 2014. Demographic and clinical information were collected and hospital live birth denominators were used to calculate incidence rates (per 1000 live births). We used the Cochran-Amitage test to assess trends. RESULTS:Surveillance identified 1484 cases. GBS was most common (532) followed by E coli (368) and viridans streptococci (280). Eleven percent of cases died and 6.3% of survivors had sequelae at discharge. All-cause (2005: 0.79; 2014: 0.77; P = .05) and E coli (2005: 0.21; 2014: 0.18; P = .25) sepsis incidence were stable. GBS incidence decreased (2005: 0.27; 2014: 0.22; P = .02). Among infants <1500 g, incidence was an order of magnitude higher for both pathogens and stable. The odds of death among infants <1500 g were similar for both pathogens but among infants ≥1500 g, the odds of death were greater for E coli cases (odds ratio: 7.0; 95% confidence interval: 2.7-18.2). CONCLUSIONS:GBS prevention efforts have not led to an increasing burden of early-onset E coli infections. However, the stable burden of E coli sepsis and associated mortality underscore the need for interventions. 10.1542/peds.2016-2013
    The global burden of paediatric and neonatal sepsis: a systematic review. Fleischmann-Struzek Carolin,Goldfarb David M,Schlattmann Peter,Schlapbach Luregn J,Reinhart Konrad,Kissoon Niranjan The Lancet. Respiratory medicine The incidence of sepsis is highest in neonates and children, yet the global burden of sepsis in these age groups has not been assessed. We reviewed available evidence from observational epidemiological studies to estimate the global burden and mortality of sepsis in neonates and children. We did a systematic review and meta-analysis of studies reporting population-based sepsis incidence in neonates and children, published between 1979 and 2016. Our search yielded 1270 studies, 23 of which met the inclusion criteria; 16 were from high-income countries and seven from middle-income countries. 15 studies from 12 countries reported complete data and were included in the meta-analysis. We found an aggregate estimate of 48 (95% CI 27-86) sepsis cases and 22 (14-33) severe sepsis cases in children per 100 000 person-years. Mortality ranged from 1% to 5% for sepsis and 9% to 20% for severe sepsis. The population-level estimate for neonatal sepsis was 2202 (95% CI 1099-4360) per 100 000 livebirths, with mortality between 11% and 19%. Extrapolating these figures on a global scale, we estimate an incidence of 3·0 million cases of sepsis in neonates and 1·2 million cases in children. Although these results confirm that sepsis is a common and frequently fatal condition affecting neonates and children globally, few population-based data are available from low-income settings and the lack of standardisation of diagnostic criteria and definition of sepsis in the reviewed studies are obstacles to the accurate estimation of global burden. Robust epidemiological monitoring to define global sepsis incidence and mortality in children is urgently needed. 10.1016/S2213-2600(18)30063-8
    Neonatal sepsis evaluation across the pond. Puopolo Karen M Archives of disease in childhood. Fetal and neonatal edition 10.1136/archdischild-2019-317840
    Neurocognitive impairment after neonatal sepsis: protocol for a systematic review and meta-analysis. Pek Jen Heng,Yap Bei Jun,Gan Ming Ying,Seethor Shu Ting Tammie,Greenberg Rachel,Hornik Christoph Paul Vincent,Tan Bobby,Lee Jan Hau,Chong Shu-Ling BMJ open INTRODUCTION:The effect of neonatal sepsis on the developing brain is not well documented. We aim to perform evidence synthesis to determine the outcome of neurodevelopmental impairment and intellectual disability among survivors of neonatal sepsis. The data gathered will inform on the long-term neurocognitive outcomes of neonates with sepsis and the measures used to document their developmental disability. METHODS AND ANALYSIS:We will perform a search based on the following parameters: neonates and infants less than 90 days old diagnosed with sepsis who had neurocognitive outcomes or measures of developmental disability reported. We will search PubMed, Cochrane Central, Embase and Web of Science for articles in English language published between January 2010 and December 2019. Clinical trials and observational studies will be included. Two independent reviewers will screen studies for eligibility. Data extraction will then be performed using a standardised form. The quality of evidence and risk of bias will be assessed using Cochrane Collaboration's tool and Risk of Bias in Non-randomised Studies of Intervention (ROBINS-I). The results will be synthesised qualitatively and pooled for meta-analysis. ETHICS AND DISSEMINATION:No formal ethical approval is required as there is no collection of primary data. This systematic review and meta-analysis will be disseminated through conference meetings and peer-reviewed publications. PROSPERO REGISTRATION NUMBER:Registration submitted CRD42020164334. 10.1136/bmjopen-2020-038816
    Premature labor and neonatal sepsis caused by Actinomyces neuii. Alsohime Fahad,Assiri Rasha A,Al-Shahrani Fatimah,Bakeet Hind,Elhazmi Malak,Somily Ali M Journal of infection and public health Actinomycosis is a rare infection in patients younger than 10years of age. It mainly affects the cervicofacial region, but many other sites of infection have been recognized. About 70% of infections are due to either Actinomyces israelii or Actinomyces gerencseriae. Actinomyces neuii was first described in 1985 in two patients with post cataract endophthalmitis, A. neuii represents 17% of clinical Actinomyces isolates. Several reports indicated a well-known association between Actinomyces infections and Intrauterine devices (IUD). We are reporting a case of neonatal sepsis due to A. neuii as a first case reported from Saudi Arabia. It was thought to be the cause of the premature labor and neonatal sepsis. The prevalence of Actinomyces infection is likely underestimated and additional premature labors and abortions could have been caused by Actinomyces infections that were never detected. More studies are needed to confirm the association of maternal Actinomyces infections with preterm labor. 10.1016/j.jiph.2018.04.001
    Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis. Sweeney Timothy E,Wynn James L,Cernada María,Serna Eva,Wong Hector R,Baker Henry V,Vento Máximo,Khatri Purvesh Journal of the Pediatric Infectious Diseases Society What’s Known on This Subject:Neonates are at increased risk for developing sepsis, but this population often exhibits ambiguous clinical signs that complicate the diagnosis of infection. No biomarker has yet shown enough diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What This Study Adds:We show that a gene-expression-based signature is an accurate objective measure of the risk of sepsis in a neonate or preterm infant, and it substantially improves diagnostic accuracy over that of commonly used laboratory-based testing. Implementation might decrease inappropriate antibiotic use. Background:Neonatal sepsis can have devastating consequences, but accurate diagnosis is difficult. As a result, up to 200 neonates with suspected sepsis are treated with empiric antibiotics for every 1 case of microbiologically confirmed sepsis. These unnecessary antibiotics enhance bacterial antibiotic resistance, increase economic costs, and alter gut microbiota composition. We recently reported an 11-gene diagnostic test for sepsis (Sepsis MetaScore) based on host whole-blood gene expression in children and adults, but this test has not been evaluated in neonates. Methods:We identified existing gene expression microarray-based cohorts of neonates with sepsis. We then tested the accuracy of the Sepsis MetaScore both alone and in combination with standard diagnostic laboratory tests in diagnosing sepsis. Results:We found 3 cohorts with a total of 213 samples from control neonates and neonates with sepsis. The Sepsis MetaScore had an area under the receiver operating characteristic curve of 0.92-0.93 in all 3 cohorts. We also found that, as a diagnostic test for sepsis, it outperformed standard laboratory measurements alone and, when used in combination with another test(s), resulted in a significant net reclassification index (0.3-0.69) in 5 of 6 comparisons. The mean point estimates for sensitivity and specificity were 95% and 60%, respectively, which, if confirmed prospectively and applied in a high-risk cohort, could reduce inappropriate antibiotic usage substantially. Conclusions:The Sepsis MetaScore had excellent diagnostic accuracy across 3 separate cohorts of neonates from 3 different countries. Further prospective targeted study will be needed before clinical application. 10.1093/jpids/pix021
    Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study. Aradhya Abhishek S,Sundaram Venkataseshan,Sachdeva Naresh,Dutta Sourabh,Saini Shiv S,Kumar Praveen European journal of pediatrics The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5-80) versus 100 (12-156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.What is known:• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.What is New:• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population. 10.1007/s00431-020-03610-x
    Early-onset neonatal sepsis is associated with a high heart rate during automatically selected stationary periods. Nguyen Nga,Vandenbroucke Laurent,Hernández Alfredo,Pham Tu,Beuchée Alain,Pladys Patrick Acta paediatrica (Oslo, Norway : 1992) AIM:This study examined the heart rate variability characteristics associated with early-onset neonatal sepsis in a prospective, observational controlled study. METHODS:Eligible patients were full-term neonates hospitalised with clinical signs that suggested early-onset sepsis and a C-reactive protein of >10 mg/L. Sepsis was considered proven in cases of symptomatic septicaemia, meningitis, pneumonia or enterocolitis. Heart rate variability parameters (n = 16) were assessed from five-, 15- and 30-minute stationary sequences automatically selected from electrocardiographic recordings performed at admission and compared with a control group using the U-test with post hoc Benjamini-Yekutieli correction. Stationary sequences corresponded to the periods with the lowest changes of heart rate variability over time. RESULTS:A total of 40 full-term infants were enrolled, including 14 with proven sepsis. The mean duration of the cardiac cycle length was lower in the proven sepsis group than in the control group (n = 11), without other significant changes in heart rate variability parameters. These durations, measured in five-minute stationary periods, were 406 (367-433) ms in proven sepsis group versus 507 (463-522) ms in the control group (p < 0.05). CONCLUSION:Early-onset neonatal sepsis was associated with a high mean heart rate measured during automatically selected stationary periods. 10.1111/apa.13782
    Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Sands Kirsty,Carvalho Maria J,Portal Edward,Thomson Kathryn,Dyer Calie,Akpulu Chinenye,Andrews Robert,Ferreira Ana,Gillespie David,Hender Thomas,Hood Kerenza,Mathias Jordan,Milton Rebecca,Nieto Maria,Taiyari Khadijeh,Chan Grace J,Bekele Delayehu,Solomon Semaria,Basu Sulagna,Chattopadhyay Pinaki,Mukherjee Suchandra,Iregbu Kenneth,Modibbo Fatima,Uwaezuoke Stella,Zahra Rabaab,Shirazi Haider,Muhammad Adil,Mazarati Jean-Baptiste,Rucogoza Aniceth,Gaju Lucie,Mehtar Shaheen,Bulabula Andre N H,Whitelaw Andrew, ,Walsh Timothy R Nature microbiology Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs. 10.1038/s41564-021-00870-7
    Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18. Wynn James Lawrence,Wilson Chris S,Hawiger Jacek,Scumpia Philip O,Marshall Andrew F,Liu Jin-Hua,Zharkikh Irina,Wong Hector R,Lahni Patrick,Benjamin John T,Plosa Erin J,Weitkamp Jörn-Hendrik,Sherwood Edward R,Moldawer Lyle L,Ungaro Ricardo,Baker Henry V,Lopez M Cecilia,McElroy Steven J,Colliou Natacha,Mohamadzadeh Mansour,Moore Daniel Jensen Proceedings of the National Academy of Sciences of the United States of America Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis. 10.1073/pnas.1515793113
    Salivary C-reactive protein, mean platelet volume and neutrophil lymphocyte ratio as diagnostic markers for neonatal sepsis. Omran Ahmed,Maaroof Abdallah,Saleh Mai H,Abdelwahab Amina Jornal de pediatria OBJECTIVE:To assess the applicability of salivary C-reactive protein, mean platelet volume, neutrophil-lymphocyte ratio, and platelet lymphocyte ratio in the diagnosis of neonatal sepsis. METHODS:Prospective case-control study of 70 full-term neonates, 35 with sepsis (20 with proven sepsis and 15 with clinical sepsis) and 35 healthy controls. Serum and salivary C-reactive protein concentrations were measured by enzyme-linked immunosorbent assay while mean platelet volume, neutrophil-lymphocyte ratio, and platelet lymphocyte ratio were measured by automated blood cell counter. RESULTS:This study showed statistically significant difference of mean salivary C-reactive protein between septic neonates and controls (12.0±4.6ng/L vs. 2.8±1.2ng/L) respectively. At a cut-off point of 3.48ng/L, salivary C-reactive protein showed 94.3% sensitivity and 80% specificity. Salivary C-reactive protein also showed good predictive accuracy for predicting elevated serum C-reactive protein values in septic neonates. Mean platelet volume and neutrophil-lymphocyte ratio showed significant difference between septic neonates and controls (10.2±1.2fL vs.8.0±0.5fL; 2.9±1.7 vs. 1.6±0.4, respectively). At a cut-off point of 10.2fL, mean platelet volume presented 80% sensitivity and specificity. At a cut-off point of 2.7, neutrophil-lymphocyte ratio presented 80% sensitivity and 57.1% specificity. CONCLUSION:This study provides support for further studies on the usefulness of salivary C-reactive protein, mean platelet volume, and neutrophil-lymphocyte ratio as diagnostic markers for neonatal sepsis. 10.1016/j.jped.2017.03.006
    Acute Kidney Injury Associated with Late-Onset Neonatal Sepsis: A Matched Cohort Study. Coggins Sarah A,Laskin Benjamin,Harris Mary Catherine,Grundmeier Robert W,Passarella Molly,McKenna Kristin J,Srinivasan Lakshmi The Journal of pediatrics OBJECTIVES:To determine incidence and severity of acute kidney injury (AKI) within 7 days of sepsis evaluation and to assess AKI duration and the association between AKI and 30-day mortality. STUDY DESIGN:Retrospective, matched cohort study in a single-center level IV neonatal intensive care unit. Eligible infants underwent sepsis evaluations at ≥72 hours of age during calendar years 2013-2018. Exposed infants (cases) were those with culture-proven sepsis and antimicrobial duration ≥5 days. Nonexposed infants (controls) were matched 1:1 to exposed infants based on gestational and corrected gestational age, and had negative sepsis evaluations with antibiotic durations <48 hours. AKI was defined by modified neonatal Kidney Disease Improving Global Outcomes criteria. Statistical analysis included Mann-Whitney and χ tests, multivariable logistic regression, and Kaplan-Meier time-to-event analysis. RESULTS:Among 203 episodes of late-onset sepsis, 40 (20%) developed AKI within 7 days after evaluation, and among 193 episodes with negative cultures, 16 (8%) resulted in AKI (P = .001). Episodes of sepsis also led to greater AKI severity, compared with nonseptic episodes (P = .007). The timing of AKI onset and AKI duration did not differ between groups. Sepsis was associated with increased odds of developing AKI (aOR, 3.0; 95% CI, 1.5-6.2; P = .002). AKI was associated with increased 30-day mortality (aOR, 4.5; 95% CI, 1.3-15.6; P = .017). CONCLUSIONS:Infants with late-onset sepsis had increased odds of AKI and greater AKI severity within 7 days of sepsis evaluation, compared with age-matched infants without sepsis. AKI was independently associated with increased 30-day mortality. Strategies to mitigate AKI in critically ill neonates with sepsis may improve outcomes. 10.1016/j.jpeds.2020.12.023
    Adjunctive therapy to treat neonatal sepsis. Esposito Susanna,Principi Nicola Expert review of clinical pharmacology : Neonatal sepsis (NS) is a very severe condition that causes significant morbidity and mortality.: To overcome the limits of antibiotic therapy and improve NS outcomes, measures chosen among those theoretically able to improve host defenses or positively interfere with deleterious immune responses could be suggested. This paper discusses the mechanisms of action of these measures, whether their efficacy in prophylaxis justifies use in NS therapy and their impact.: NS remains a relevant problem despite the availability of antibiotics effective against the most common agents and the introduction of effective preventive measures such as group B prenatal screening and intrapartum antibiotic prophylaxis. This explains why attempts to introduce new prophylactic and therapeutic measures have been made. Unfortunately, none of the measures suggested and tested to date can be considered a definitive advance. It is highly likely that in the future, new measures will be proposed according to the increase in the knowledge of the characteristics of immune system function in preterm infants and the methods to modulate unproper immune responses. 10.1080/17512433.2020.1699790
    Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Fleischmann Carolin,Reichert Felix,Cassini Alessandro,Horner Rosa,Harder Thomas,Markwart Robby,Tröndle Marc,Savova Yoanna,Kissoon Niranjan,Schlattmann Peter,Reinhart Konrad,Allegranzi Benedetta,Eckmanns Tim Archives of disease in childhood BACKGROUND:Neonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide. METHODS:We performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979-May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level. RESULTS:The search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009-2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias. CONCLUSION:Neonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide. 10.1136/archdischild-2020-320217
    Diagnostics for neonatal sepsis: current approaches and future directions. Iroh Tam Pui-Ying,Bendel Catherine M Pediatric research Progress has been made in the reduction of morbidity and mortality from neonatal sepsis. However, diagnosis continues to rely primarily on conventional microbiologic techniques, which can be inaccurate. The objective of this review is to provide the clinician with an overview of the current information available on diagnosing this condition. We review currently available diagnostic approaches for documenting neonatal sepsis and also describe novel approaches for diagnosing infection in neonates who are under development and investigation. Substantial progress has been made with molecular approaches and further development of non-culture-based methods offer promise. The potential ability to incorporate antimicrobial resistance gene testing in addition to pathogen identification may provide a venue to incorporate a predominantly molecular platform into a larger program of neonatal care. 10.1038/pr.2017.134
    Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network. Li Grace,Bielicki Julia Anna,Ahmed A S M Nawshad Uddin,Islam Mohammad Shahidul,Berezin Eitan Naaman,Gallacci Clery B,Guinsburg Ruth,da Silva Figueiredo Carlos Eduardo,Santarone Vieira Rosilene,Silva Andre Ricardo,Teixeira Cristiane,Turner Paul,Nhan Ladin,Orrego Jaime,Pérez Paola Marsela,Qi Lifeng,Papaevangelou Vassiliki,Triantafyllidou Pinelope,Iosifidis Elias,Roilides Emmanuel,Sarafidis Kosmas,Jinka Dasaratha Ramaiah,Nayakanti Raghuprakash Reddy,Kumar Praveen,Gautam Vikas,Prakash Vinayagam,Seeralar Arasar,Murki Srinivas,Kandraju Hemasree,Singh Sanjeev,Kumar Anil,Lewis Leslie,Pukayastha Jayashree,Nangia Sushma,K N Yogesha,Chaurasia Suman,Chellani Harish,Obaro Stephen,Dramowski Angela,Bekker Adrie,Whitelaw Andrew,Thomas Reenu,Velaphi Sithembiso Christopher,Ballot Daynia Elizabeth,Nana Trusha,Reubenson Gary,Fredericks Joy,Anugulruengkitt Suvaporn,Sirisub Anongnart,Wong Pimol,Lochindarat Sorasak,Boonkasidecha Suppawat,Preedisripipat Kanchana,Cressey Tim R,Paopongsawan Pongsatorn,Lumbiganon Pagakrong,Pongpanut Dounghatai,Sukrakanchana Pra-Ornsuda,Musoke Philippa,Olson Linus,Larsson Mattias,Heath Paul T,Sharland Michael Archives of disease in childhood OBJECTIVE:To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN:A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING:39 NNUs from 12 countries. PATIENTS:Any neonate admitted to one of the participating NNUs. INTERVENTIONS:This was an observational cohort study. RESULTS:The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION:AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally. 10.1136/archdischild-2019-316816
    Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use. van Herk Wendy,Stocker Martin,van Rossum Annemarie M C The Journal of infection Early diagnosis and timely treatment of early onset neonatal sepsis (EOS) are essential to prevent life threatening complications. Subtle, nonspecific clinical presentation and low predictive values of biomarkers complicate early diagnosis. This uncertainty commonly results in unnecessary and prolonged empiric antibiotic treatment. Annually, approximately 395,000 neonates (7.9% of live term births) are treated for suspected EOS in the European Union, while the incidence of proven EOS varies between 0.01 and 0.53 per 1000 live births. Adherence to guidelines for the management of suspicion of EOS is poor. Pragmatic approaches to minimise overtreatment in neonates with suspected EOS, using combined stratified risk algorithms, based on maternal and perinatal risk factors, clinical characteristics of the neonate and sequential biomarkers are promising. 10.1016/j.jinf.2016.04.026
    Neutrophil CD64 as a diagnostic marker for neonatal sepsis: Meta-analysis. Dai Ji,Jiang Wenjie,Min Zhigang,Yang Jian,Tan Yongfei,Ma Tieliang,Ge Zhijun Advances in clinical and experimental medicine : official organ Wroclaw Medical University BACKGROUND:Neutrophil CD64 (nCD64) is a promising marker for diagnosing bacterial infections. Several studies have investigated the performance of nCD64 for diagnosing neonatal sepsis and the results are variable. Interest in nCD64 for detecting serious bacterial infections is increasing rapidly. OBJECTIVES:The aim of the present study was to carry out a meta-analysis to systematically evaluate the diagnostic accuracy of nCD64 in neonatal sepsis. As far as the authors know, no previous studies have undertaken this. MATERIAL AND METHODS:A review of studies from Pubmed, Embase and the Cochrane Library, from inception through June 2015, found 7 studies (involving 2213 neonates) fulfilling the inclusion criteria. These 7 studies were subjected to a bivariate meta-analysis of sensitivity and specificity and a summary receiveroperating characteristic (SROC) curve; I2 was used to test heterogeneity, and the source of heterogeneity was investigated by influence analysis and meta-regression. RESULTS:The pooled sensitivity and specificity were 80% (95%CI, 69-88%) and 83% (95%CI, 71-90%), respectively. The area under the SROC curve (AUC) was 0.88 (95%CI, 0.85-0.91). The studies had substantial heterogeneity (I2 = 87.1%). CONCLUSIONS:The results showed that nCD64 is a reliable biomarker for diagnosing neonatal sepsis (AUC = 0.88). 10.17219/acem/58782
    Neonatal Sepsis and Its Associated Factors Among Neonates Admitted to Neonatal Intensive Care Units in Primary Hospitals in Central Gondar Zone, Northwest Ethiopia, 2019. Agnche Zelalem,Yenus Yeshita Hedja,Abdela Gonete Kedir Infection and drug resistance Background:Neonatal sepsis contributes substantially to neonatal morbidity and mortality and is an ongoing major global public health challenge particularly in developing countries. Studies conducted on the proportion and risk factors of neonatal sepsis in Ethiopia are from referral hospitals, which may not be generalized to primary health care units where a significant proportion of mothers give birth in these health facilities. This study sought to determine the proportion of clinical neonatal sepsis and associated factors in the study areas. Methods:Institutional-based cross-sectional study was conducted from March to April 2019, in Amhara regional state, central Gondar zone public primary hospitals in Ethiopia. A total of 352 subjects (mother-neonate pairs) were selected using a systematic random sampling technique and pre-tested and structured questionnaires were used to collect data. Multivariable logistic regression analysis was fitted to identify factors associated with neonatal sepsis. Adjusted odds ratio (AOR) with the corresponding 95% confidence interval (CI) was used to show the strength of associations and variables with p-values of <0.05 were considered as statistically significant. Results:The overall proportion of neonatal sepsis was 64.8% (95% CI (59.2, 69.2)). Being male neonate (AOR=3.7; 95% CI (1.76, 7.89)), history of urinary tract infections during the index pregnancy (AOR =6, 26; 95% CI (1.16, 33.62)), frequency of per-vaginal examination greater than three during labor and delivery (AOR=6.06; 95% CI (2.45, 14.99)), neonatal resuscitation at birth (AOR=6.1; 95% CI (1.71, 21.84)), place of delivery at the health center (AOR=3.05; 95% CI (1.19, 7.79)), lack of training of health workers on neonatal resuscitation and infection prevention practices (AOR=2.14; 95% CI (1.04, 4.44)), late age of neonate at onset of illness (AOR=0.05; 95% CI (0.01, 0.21)) and maternal age of 30-34 years (AOR=0.19; 95% CI (0.047, 0.81)) were significantly associated with neonatal sepsis. Conclusion:The proportion of neonatal sepsis is high. Maternal, neonatal, and health service related factors were identified for neonatal sepsis. Therefore, training of health workers, provision of health care services as per standards, and monitoring and evaluation of obstetrical/neonatal care during labor and delivery are mandatory. 10.2147/IDR.S276678
    Vitamin D deficiency and vitamin D receptor variants in mothers and their neonates are risk factors for neonatal sepsis. Tayel Safaa I,Soliman Shimaa E,Elsayed Hanan M Steroids BACKGROUND AND AIM:Increasing prevalence of neonatal sepsis in recent years catch attention to early prevention and management. Vitamin D receptor (VDR) polymorphism can modulate VDR expression level that greatly influences immunity and susceptibility to microbial infections. We aimed to investigate the association of VDR polymorphism at FokI, rs2228570 T/C, and TaqI, rs731236 C/T gene with serum 25-hydroxyvitamin D level and risk of neonatal sepsis. METHODS:This work carried on 160 subjects classified into 80 cases (40 mothers and their 40 septic neonates) and 80 healthy controls (40 volunteer mothers and their 40 healthy neonates). Genotyping of VDR polymorphisms were assayed by real-time PCR and serum 25-hydroxyvitamin D level and hs-CRP were measured by ELISA. RESULTS:Vitamin D deficiency was observed in mothers of cases compared with healthy ones (p = <0.001) and in septic neonates versus healthy ones (p = <0.001). Septic neonates had much higher VDR FokI TT genotype (p = 0.014) and T allele (p = 0.003) versus healthy ones. TT genotype and T allele could increase the risk of sepsis with OR 95% CI [4.804 (1.4-16.4)] and [2.786 (1.4-5.7)] respectively while VDR TaqI showed no association with sepsis. There was a strong LD between FokI and TaqI in sepsis cases. In sepsis, T/T genotype at FokI had significantly lower vitamin D (p = <0.001). CONCLUSION:Vitamin D deficiency in mothers/neonates is a risk factor for neonatal sepsis. VDR FokI T allele had lower 25-hydroxyvitamin D level that may predispose to sepsis hazards. 10.1016/j.steroids.2018.03.003
    Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin. Hansen Richard,Gibson Sophie,De Paiva Alves Eduardo,Goddard Mark,MacLaren Andrew,Karcher Anne Marie,Berry Susan,Collie-Duguid Elaina S R,El-Omar Emad,Munro Mike,Hold Georgina L Scientific reports Hyperbilirubinemia is so common in newborns as to be termed physiological. The most common bacteria involved in early-onset neonatal sepsis are Streptococcus agalactiae, commonly called Group B Streptococcus (GBS). Whilst previous studies show bilirubin has antioxidant properties and is beneficial in endotoxic shock, little thought has been given to whether bilirubin might have antibacterial properties. In this study, we performed a transcriptomic and proteomic assessment of GBS cultured in the presence/absence of bilirubin. Our analysis revealed that increasing levels of bilirubin (>100 µmol/L) negatively correlated with GBS growth (18% reduction from 0-400 µmol/L on plate model, p < 0.001; 33% reduction from 0-100 µmol/L in liquid model, p = 0.02). Transcriptome analysis demonstrated 19 differentially expressed genes, almost exclusively up-regulated in the presence of bilirubin. Proteomic analysis identified 12 differentially expressed proteins, half over-expressed in the presence of bilirubin. Functional analysis using Gene Ontology and KEGG pathways revealed a differential expression of genes involved in transport and carbohydrate metabolism, suggesting bilirubin may impact on substrate utilisation. The data improve our understanding of the mechanisms modulating GBS survival in neonatal hyperbilirubinemia and suggest physiological jaundice may have an evolutionary role in protection against early-onset neonatal sepsis. 10.1038/s41598-018-24811-3
    Ratio of neutrophilic CD64 and monocytic HLA-DR: A novel parameter in diagnosis and prognostication of neonatal sepsis. Pradhan Richeek,Jain Paresh,Paria Anshuman,Saha Anindya,Sahoo Jagdish,Sen Anway,Mukherjee Suchandra,Som Tapas,Hazra Avijit,Warner Noel,Singh Arun K,Chatterjee Mitali Cytometry. Part B, Clinical cytometry OBJECTIVE:Approaches to monitoring of sepsis have traditionally relied upon the pro-inflammatory component of the sepsis response. This study evaluated the diagnostic and prognostic potential of the ratio of neutrophilic CD64 (nCD64) and monocytic HLA-DR (mHLA-DR) median fluorescence index in monitoring of neonatal sepsis. METHODS:Blood from 100 neonates suspected of sepsis and 29 healthy controls was collected on clinical suspicion of sepsis, and the expression of nCD64, mHLA-DR was evaluated by Flow Cytometry; thereby, a derived parameter "Sepsis index," SI = nCD64/mHLA-DR × 100 was estimated. RESULTS:At day 1, sensitivity and specificity to detect sepsis using nCD64 was 73.01% and 89.18%, respectively, while for SI it was 73.01% and 72.22%, respectively. On Kaplan-Meier analysis, neonates with SI > cut-off showed a higher 30 day-mortality than those with low SI (P = 0.096). On multivariate analysis, the factor associated with mortality in our cohort was Apgar score ≤3, while SI showed a trend toward significance. CONCLUSIONS:At day1, nCD64 is useful for the diagnosis of neonatal sepsis whereas mHLA-DR is beneficial for monitoring patients at a later time point. The SI is a marker of moderate diagnostic sensitivity and supplements the current arsenal of laboratory investigations to detect neonatal sepsis. As a marker of prognosis, a high SI shows a trend towards greater mortality. © 2015 Clinical Cytometry Society. 10.1002/cyto.b.21244
    Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies. Stoll Barbara J,Puopolo Karen M,Hansen Nellie I,Sánchez Pablo J,Bell Edward F,Carlo Waldemar A,Cotten C Michael,D'Angio Carl T,Kazzi S Nadya J,Poindexter Brenda B,Van Meurs Krisa P,Hale Ellen C,Collins Monica V,Das Abhik,Baker Carol J,Wyckoff Myra H,Yoder Bradley A,Watterberg Kristi L,Walsh Michele C,Devaskar Uday,Laptook Abbot R,Sokol Gregory M,Schrag Stephanie J,Higgins Rosemary D, JAMA pediatrics Importance:Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective:To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants:This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures:Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results:A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance:In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens. 10.1001/jamapediatrics.2020.0593
    Neutrophil Volume, conductivity and scatter (VCS) as a screening tool in neonatal sepsis. Nesargi Prerana,Niranjan H S,Bandiya Prathik,Benakappa Naveen Scientific reports The initial evaluation of a suspected sepsis in a neonate is always challenging. There are many methods to screen a neonate with suspected sepsis. One of newer method is to assess the changes in neutrophil volume conductivity and scatter. The objective of this study was to establish changes in Neutrophil volume conductivity scatter (VCS) in neonatal sepsis and to determine appropriate cut off levels using receiver operating characteristic (ROC) curves. Neonates with suspected sepsis were evaluated with blood counts, culture and neutrophil VCS parameters. Based on these parameters neonates were classified into sepsis group (Blood culture positive), Probable sepsis group (clinical course consistent with sepsis and positive sepsis screen and negative blood culture), No sepsis group (Clinical course not suggestive of sepsis with negative sepsis screen and blood culture). A total of 304 neonates were included in the study of which 144 were in sepsis group and 160 in no sepsis group respectively. Among the neutrophil VCS parameters there was significant difference between the groups with respect to mean neutrophil volume (MNV) and volume distribution width (VDW) (180 vs 163 vs 150) (p < 0.01). MNV and VDW had good sensitivity (95%, 82%) and specificity (86%, 74%) for diagnosis of sepsis. In conclusion, Neutrophil VCS parameters, especially MNV, can be incorporated with other sepsis screen parameters in diagnosis of neonatal sepsis. 10.1038/s41598-020-61434-z
    The Utility of Soluble CD14 Subtype in Early Diagnosis of Culture-Proven Early-Onset Neonatal Sepsis and Prediction of Outcome. Gad Ghada I,Shinkar Dina M,Kamel El-Din Manal M,Nagi Hoda M American journal of perinatology OBJECTIVE:This study aimed to evaluate soluble cluster of differentiation 14 subtype (sCD14-ST), also named presepsin, as an early marker for the diagnosis of culture-proven early-onset sepsis (EOS) in neonates and to assess its relation to disease severity and mortality. STUDY DESIGN:Out of 60 neonates with risk factors of EOS, 31 neonates were diagnosed as having culture-proven EOS. They were compared with 20 nonseptic controls. We obtained blood samples on day 1 of life for sCD14-ST measurement and sepsis screening. Blood samples were repeated on day 3 in EOS neonates. RESULTS:sCD14-ST was significantly higher in EOS neonates than controls ( < 0.001). Neonates who later developed septic shock had significantly higher day 1 sCD14-ST level than those who did not ( < 0.001). Furthermore, neonates who died had significantly higher day 1 sCD14-ST than survivors ( < 0.001). On day 3, there was a significant decline in sCD14-ST levels than initial levels among survivors. There was a significant positive correlation between day 1 sCD14-ST level and Tollner's sepsis severity score. CONCLUSION:sCD14-ST could be used as a powerful diagnostic and prognostic marker of EOS. Its quantitative measurement at birth could be a good predictor of sepsis severity and mortality. 10.1055/s-0039-1683863
    A Study of Red Cell Distribution Width in Neonatal Sepsis. Ellahony Dalia Monir,El-Mekkawy Muhammad S,Farag Marwa M Pediatric emergency care OBJECTIVES:The objective of this study was to evaluate a new nontraditional value of the red cell distribution width (RDW) in predicting the clinical outcome of neonatal sepsis. METHODS:In this retrospective study, data were collected from the medical files of 500 full-term neonates with a diagnosis of early onset or late onset sepsis. Baseline RDW and other traditional biomarkers, including C-reactive protein (CRP), total leucocytic count, and platelet count were analyzed in light of the clinical data. The primary outcome was 30-day mortality. RESULTS:Red cell distribution width was significantly higher in nonsurvivors compared with survivors (P < 0.0001). Red cell distribution width was significantly elevated in infants with septic shock compared with those having severe sepsis and those with sepsis (P < 0.0001). A strong positive correlation was found between RDW and CRP (r = 0.8; P <0.0001). Red cell distribution width had an area under the receiver operating characteristic curve of 0.75 for prediction of mortality, which was almost equal to that of CRP and platelet count. Furthermore, logistic regression analysis showed a positive association of RDW with mortality (odds ratio, 1.31; 95% confidence interval, 1.241-1.399). CONCLUSIONS:Red cell distribution width is a useful prognostic marker in neonatal sepsis. Larger prospective studies are required to confirm the value of this routinely available marker in this category of patients. 10.1097/PEC.0000000000001319
    Using newborn screening analytes to identify cases of neonatal sepsis. Fell Deshayne B,Hawken Steven,Wong Coralie A,Wilson Lindsay A,Murphy Malia S Q,Chakraborty Pranesh,Lacaze-Masmonteil Thierry,Potter Beth K,Wilson Kumanan Scientific reports Neonatal sepsis is associated with high mortality and morbidity, yet challenges with available diagnostic approaches can lead to delays in therapy. Our study assessed whether newborn screening analytes could be utilized to identify associations with neonatal sepsis. We linked a newborn screening registry with health databases to identify cases of sepsis among infants born in Ontario from 2010-2015. Correlations between sepsis and screening analytes were examined within three gestational age groups (early preterm: <34 weeks; late preterm: 34-36 weeks; term: ≥37 weeks), using multivariable logistic regression models. We started with a model containing only clinical factors, then added groups of screening analytes. Among 793,128 infants, 4,794 were diagnosed with sepsis during the neonatal period. Clinical variables alone or in combination with hemoglobin values were not strongly predictive of neonatal sepsis among infants born at term or late preterm. However, model fit improved considerably after adding markers of thyroid and adrenal function, acyl-carnitines, and amino acids. Among infants born at early preterm gestation, neither clinical variables alone nor models incorporating screening analytes adequately predicted neonatal sepsis. The combination of clinical variables and newborn screening analytes may have utility in identifying term or late preterm infants at risk for neonatal sepsis. 10.1038/s41598-017-18371-1
    Meta-analysis of diagnostic accuracy of neutrophil CD64 for neonatal sepsis. Shi Jing,Tang Jun,Chen Dapeng Italian journal of pediatrics BACKGROUND:The aim of this study was to systematically evaluate the diagnostic performance of nCD64 for neonatal sepsis. METHODS:Computer retrieval was conducted for the databases of PubMed, Embase, and Springer databases up to March 18, 2015 to select the relevant studies on nCD64 and neonatal sepsis. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95 % confidence intervals (CI) for diagnostic efficiency of nCD64 were pooled. In addition, the summary receiver operating characteristic (SROC) curve was also conducted based on the sensitivity and specificity. RESULTS:Seventeen studies including 3478 participants were included in this meta-analysis. The overall pooled sensitivity, specificity, PLR, NLR and DOR were 0.77 (95 % CI: 0.74-0.79), 0.74 (95 % CI: 0.72-0.75), 3.58 (95 % CI: 2.85-4.49), 0.29 (95 % CI: 0.22-0.37) and 15.18 (95 % CI: 9.75-23.62), respectively. In addition, the area under the SROC curve (AUC) was 0.8666, and no threshold effect was found based on the Spearman correlation analysis (P = 0.616). Besides, subgroup analysis showed higher sensitivity, specificity and AUC in term infants and proven infection group than those in preterm infants and clinical infection group, respectively. CONCLUSIONS:The n CD64 expression alone is not a satisfactory marker for diagnosing neonatal sepsis with relatively low sensitivity, specificity, PLR and NLR, in spite of relatively high SROC area. Therefore, the n CD64 expression used in diagnosis of neonatal sepsis should be treated with caution. 10.1186/s13052-016-0268-1
    Utility of cytokines to predict neonatal sepsis. Ye Qing,Du Li-Zhong,Shao Wen-Xia,Shang Shi-Qiang Pediatric research BACKGROUND:Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. METHODS:Serum inflammatory cytokine levels were evaluated in the early stage of neonatal sepsis and after antimicrobial treatment. Receiver operating characteristic curves assessed the diagnostic value of cytokines. We performed multiple logistic regression analysis to characterize the role of each cytokine independently for infants with culture proven sepsis. RESULTS:C-reactive protein, interleukin (IL)-6, IL-10 and IL-6/IL-10 levels were significantly elevated in neonatal sepsis when compared with the control group and there were 1.4 (95% confidence interval (CI): 1.2-1.5), 4.9 (95% CI: 4.6-5.1), 5.1 (95% CI: 4.5-5.6), and 10.2 (95% CI: 9.2-11.1) fold greater odds, respectively, to predict neonatal sepsis when increased. After effective treatment, median IL-6 (pretreatment value: 263.0 pg/ml and post-treatment value: 7.4 pg/ml) and IL-6/IL-10 levels (pretreatment value: 16.6 and post-treatment value: 1.4) significantly decreased. The areas under the curve for IL-6, IL-10, IL-6/IL-10 and C-reactive protein for differential diagnosis were 0.98, 0.82, 0.90, and 0.88, respectively. CONCLUSION:IL-6 and IL-6/IL-10 outperformed C-reactive protein to diagnose neonatal sepsis. Of the cytokines studied, IL-6 was the most sensitive, whereas IL-6/IL-10 was the most specific predictor of neonatal sepsis. 10.1038/pr.2016.267
    Incidence of fever in labor and risk of neonatal sepsis. Towers Craig V,Yates Angela,Zite Nikki,Smith Casey,Chernicky Lindsey,Howard Bobby American journal of obstetrics and gynecology BACKGROUND:The current recommendation regarding the management of a term newborn delivered of a mother with an intrapartum fever or a diagnosis of clinical chorioamnionitis is that the neonate should have baseline laboratory work drawn along with blood cultures and be universally treated with antibiotics until culture results return. These guidelines report that the rate of intrapartum fever is about 3%; however, a few large studies suggest that the rate is higher at about 7%. OBJECTIVE:We sought to prospectively evaluate the rate of fever during labor in a large number of deliveries and determine the rate of early-onset neonatal sepsis in newborns delivered from mothers with an intrapartum fever compared with newborns delivered from mothers without intrapartum fever. STUDY DESIGN:This was a prospective cohort study of all temperatures obtained in women in labor from Jan. 1, 2011, through June 30, 2014. Every patient with a fever of ≥38°C at ≥36 weeks' gestation was evaluated for gestational age, parity, spontaneous or induced labor, group B streptococcus status, regional anesthesia, mode of delivery, treatment with intrapartum antibiotics, and whether a clinical diagnosis of chorioamnionitis was made by the managing physician. Neonates were assessed for blood culture results, neonatal intensive care unit admission, length of stay, and any major newborn complications. Statistical analysis involved χ, Fisher exact, and Student t test. RESULTS:A total of 412 patients (6.8%; 95% confidence interval, 6.2-7.5%) developed a fever in 6057 deliveries at ≥36 weeks' gestation. No cases of maternal sepsis occurred. Of the 417 newborns (5 sets of twins), only 1 (0.24%; 95% confidence interval, 0.01-1.3%) developed early-onset neonatal sepsis with a positive blood culture for Escherichia coli. There were 4 cases (0.07%; 95% confidence interval, 0.02-0.18%) of early-onset neonatal sepsis in the 5697 newborns (52 sets of twins) delivered from mothers who were not febrile and this difference was not significant (P = .3). The positive blood cultures in these 4 neonates were 3 group B streptococcus and 1 Enterococcus. The overall rate of early-onset neonatal sepsis in this population of newborns delivered at ≥36 weeks' gestation was 0.82/1000 deliveries. CONCLUSION:The incidence of an intrapartum fever of ≥38°C in pregnancies at ≥36 weeks' gestation is common at 6.8% and this is consistent with the findings of a few other large retrospective studies. The rate of an intrapartum fever occurs in approximately 1 in 15 women in labor. The risk of neonatal sepsis in newborns delivered of mothers with intrapartum fever or a diagnosis of clinical chorioamnionitis is low at 0.24%, a rate that is <1 in 400. The recommendation for universal laboratory work, cultures, and antibiotic treatment pending culture results for this newborn population needs further examination. 10.1016/j.ajog.2017.02.022
    Biomarkers for diagnosis of neonatal sepsis: a literature review. Sharma Deepak,Farahbakhsh Nazanin,Shastri Sweta,Sharma Pradeep The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Sepsis is an important cause of mortality and morbidity in neonatal populations. There has been constant search of an ideal sepsis biomarker that have high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), so that both the diagnosis and exclusion of neonatal sepsis can be made at the earliest possible and appropriate antibiotics can be started to neonate. Ideal sepsis biomarker will help in guiding us when not to start antibiotics in case of suspect sepsis and total duration of antibiotics course in case of proven sepsis. There are numerous sepsis biomarkers that have been evaluated for early detection of neonatal sepsis but till date there is no single ideal biomarker that fulfills all essential criteria's for being an ideal biomarker. The most commonly used biomarkers are C-reactive protein (CRP) and procalcitonin (PCT), but both have shown varied sensitivity, specificity, PPV and NPV in different studies. We conducted literature search for various neonatal sepsis biomarkers and this review article will cover briefly all the markers with current available evidence. 10.1080/14767058.2017.1322060
    Utility of serum resistin in the diagnosis of neonatal sepsis and prediction of disease severity in term and late preterm infants. Khattab Ahmed Anwar,El-Mekkawy Muhammad Said,Helwa Mohamed Ahmed,Omar Ehab Seif Journal of perinatal medicine Introduction Resistin is a proinflammatory hormone recently proposed as a sepsis biomarker. Our aim was to evaluate the diagnostic and prognostic values of this marker in neonatal sepsis. Methods This is a prospective observational study that includes 60 term and late preterm neonates with proven and possible sepsis besides 30 healthy controls. Resistin and other biomarkers, like C-reactive protein (CRP), were measured within 2 h of neonatal intensive care unit (NICU) admission. Infants were monitored and the primary outcome was 30-day mortality. Results Resistin was higher among septic neonates compared with controls (P<0.001). Resistin had an area under the receiver operating characteristic (ROC) curve of 0.994 for differentiating septic infants from controls. The area under the curve (AUC) for differentiating infants with culture-proven sepsis from controls was 0.999 compared with an AUC of 1 for CRP. The other markers, like platelet count, were inferior to resistin and CRP. Resistin was positively correlated with CRP [Spearman's correlation coefficient (rs)=0.55, P<0.001]. No significant differences in resistin levels were noted between survivors and non-survivors but resistin was higher among infants with severe sepsis (P=0.015) and among those who needed mechanical ventilation (P<0.001). Conclusion Resistin is useful for the diagnosis of neonatal sepsis. Resistin failed to predict mortality but was associated with indicators of disease severity. 10.1515/jpm-2018-0018
    Neonatal Sepsis: Clinical characteristics, Epidemiology and Antibiotic Sensitivity Pattern of the Bacterial Pathogens in Neonatal Intensive Care Unit of a Tertiary Care Hospital. Moni S C,Mollah A H,Banerjee M,Khan T H,Sejuti A,Morshed S S Mymensingh medical journal : MMJ Neonatal sepsis, a major newborn killer worldwide exhibits wide spectrum of clinical manifestations. Epidemiology and aetiological organisms vary with geographical area and time. Objective of the study was to study clinical characteristics, epidemiology, bacterial aetiology and drug sensitivity pattern of isolated organisms in Neonatal Intensive Care Unit (NICU), Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh. This observational cross sectional study was carried out in NICU, DMCH from January 2014 to June 2015. The inclusion criteria were newborns having features of sepsis at admission or developing such features afterwards when admitted for other indications. A blood sample was collected aseptically immediately after clinical diagnosis and was sent for relevant laboratory investigations. Sample for culture sensitivity was inoculated bedside to culture bottle and sent to department of microbiology. The newborns were followed up till hospital discharge or death. All information regarding history, laboratory findings and follow up were recorded in a structured questionnaire. Of the 200 neonates, 59% were diagnosed as having late onset sepsis (LONS). Premature and low birth weight (LBW) babies mostly suffered from LONS. Respiratory distress, tachycardia, lethargy were the predominant symptoms in both early and late sepsis. Blood culture yielded growth in 55% of the septic newborns. Klebsiella pneumoniae was the predominant organism in both early and late sepsis. Most of the Gram negative bacteria were sensitive to colistin, meropenem and imipenem. Case fatality was 24.39% and 34.74% in early and late sepsis respectively.
    [Clinical value of blood lactate in predicting the prognosis of neonatal sepsis]. Sun Yu-Shan,Yu Jia-Lin Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To explore the clinical value of arterial blood lactate level in predicting the prognosis of neonatal sepsis. METHODS:The clinical data of 301 cases of neonatal sepsis were collected, which mainly included biochemical indicators such as blood lactate on admission, C-reactive protein, and procalcitonin. ROC curves were plotted to evaluate the value of lactate level on admission in predicting the prognosis of neonatal sepsis. RESULTS:The mortality rate was significantly higher for full-term infants in the severely-elevated lactate group than in the mildly-elevated lactate group and the normal lactate group (26.1% vs 3.1% and 0%; P<0.017). The poor prognosis group had a significantly increased lactate level on admission compared with the good prognosis group (6.5±5.1 mmol/L vs 3.6±1.7 mmol/L; P<0.05). The sensitivity and specificity of blood lactate level on admission (cutoff value: 6.15 mmol/L) were 0.545 and 0.919 respectively, in predicting the prognosis of neonatal sepsis. CONCLUSIONS:Early blood lactate level can be used as a biochemical parameter to predict the prognosis of neonatal sepsis as it has a high specificity but a low sensitivity.
    Active antibiotic discontinuation in suspected but not confirmed early-onset neonatal sepsis-A quality improvement initiative. Dretvik Thomas,Solevåg Anne Lee,Finvåg Andreas,Størdal Eline Hasselgård,Størdal Ketil,Klingenberg Claus Acta paediatrica (Oslo, Norway : 1992) AIM:To study whether a simple targeted intervention could reduce unwarranted antibiotic treatment in near-term and term neonates with suspected, but not confirmed early-onset sepsis. METHODS:A quality improvement initiative in three Norwegian neonatal intensive care units. The intervention included an inter-hospital clinical practice guideline for discontinuing antibiotics after 36-48 hours if sepsis was no longer suspected and blood cultures were negative in neonates ≥ 34+0 weeks of gestation. Two units used procalcitonin in decision-making. We compared data 12-14 months before and after guideline implementation. The results are presented as median with interquartile ranges. RESULTS:A total of 284 infants (2.5% of all births ≥ 34+0 weeks of gestation) received antibiotics before and 195 (1.8%) after guideline implementation (P = .0018). The two units that used procalcitonin discontinued antibiotics earlier after guideline implementation than the unit without procalcitonin. Neonates not diagnosed with sepsis were treated 49 (31-84) hours before and 48 (36-72) hours after guideline implementation (P = .68). In all infants, including those diagnosed with sepsis, antibiotic treatment duration was reduced from 108 (60-144) to 96 (48-120) hours (P = .013). CONCLUSION:Antibiotic treatment duration for suspected, but not confirmed early-onset sepsis did not change. However, treatment duration for all infants and the proportion of infants commenced on antibiotics were reduced. 10.1111/apa.15202
    Risk factors associated with late-onset neonatal sepsis Arias-Arellano Santiago,Cáceres-Aucatoma Freud,Geyson Déley,Segarra-Galarza Katy Revista medica del Instituto Mexicano del Seguro Social Background:Sepsis is one of the main causes of morbidity and mortality in neonates. Objective:To identify the risk factors for neonatal sepsis in a neonatal unit from March to October, 2016. Methods:Case-control study. The factors analyzed were: a) neonatal factors such as: type of delivery, sex, birth weight, gestational age, criteria for systemic inflammatory response syndrome, type of sepsis (early or late) and blood culture result; B) invasive methods such as: central catheterization, total parenteral nutrition, umbilical catheterization and mechanical ventilation; C) maternal factors such as: number of prenatal controls, infection during pregnancy, premature rupture of membranes, maternal age and maternal fever. Odds Ratio was used to determine association. Results:For the development of early-onset sepsis, significant risk factors were: thermodynamic imbalance, tachycardia and maternal fever. With regard to late-onset sepsis, significant associations were found for thermodynamic imbalance, umbilical catheterization, mechanical ventilation and insufficient prenatal care. Conclusions:Thermodynamic imbalance, tachycardia, mechanical ventilation, umbilical catheterization, maternal fever, and insufficient prenatal care were the probable risk factors associated with neonatal sepsis.
    Risk factors of neonatal sepsis in India: A systematic review and meta-analysis. Murthy Shruti,Godinho Myron Anthony,Guddattu Vasudeva,Lewis Leslie Edward Simon,Nair N Sreekumaran PloS one BACKGROUND:The incidence of neonatal sepsis in India is the highest in the world. Evidence regarding its risk factors can guide clinical practice and prevention strategies. OBJECTIVE:To review, assess and synthesize the available literature from India on the risk factors of sepsis among neonates. METHODOLOGY:A systematic review was conducted. We searched PubMed, CINAHL, Scopus, Web of Science, Popline, IndMed, Indian Science Abstracts and Google Scholar from inception up to March 23, 2018 to identify observational analytical studies reporting on risk factors of laboratory-confirmed neonatal sepsis in India. Two authors independently screened studies (title, abstract and full-text stages), extracted data, and assessed quality. A random-effects meta-analysis was performed as substantial heterogeneity was anticipated. Subgroup and sensitivity analyses were additionally performed. Effect size in our review included odds ratio and standardized mean difference. RESULTS:Fifteen studies were included from 11,009 records, of which nine were prospective in design. Birthweight and gestational age at delivery were the most frequently reported factors. On meta-analyses, it was found that male sex (OR: 1.3, 95% CI: 1.02, 1.68), out born neonates (OR: 5.5, 95% CI: 2.39, 12.49), need for artificial ventilation (OR: 5.61; 95% CI: 8.21, 41.18), gestational age <37 weeks (OR: 2.05; 95% CI:1.40, 2.99) and premature rupture of membranes (OR:11.14, 95% CI: 5.54, 22.38) emerged as risk factors for neonatal sepsis. Included studies scored lowest on exposure assessment and confounding adjustment, which limited comparability. Inadequacy and variation in definitions and methodology affected the quality of included studies and increased heterogeneity. CONCLUSIONS:Male neonates, outborn admissions, need for artificial ventilation, gestational age <37 weeks and premature rupture of membranes are risk factors for sepsis among neonates in India. Robustly designed and reported research is urgently needed to confirm the role of other risk factors of neonatal sepsis in India. 10.1371/journal.pone.0215683
    Is Lower Vitamin D Level Associated with Increased Risk of Neonatal Sepsis? A Prospective Cohort Study. Behera Chinmay Kumar,Sahoo Jagdish Prasad,Patra Saumya Darshana,Jena Pratap Kumar Indian journal of pediatrics OBJECTIVE:To evaluate the effect of maternal/ neonatal vitamin D levels on culture positive neonatal sepsis. METHODS:This prospective cohort study was conducted in the NICU of a tertiary care teaching hospital in Odisha, Eastern India from January 2015 through December 2016. Forty (40) neonates with culture positive sepsis were included in the study group. Forty (40) healthy neonates admitted for evaluation of neonatal jaundice who are similar in gender, gestational age, postnatal age and without any clinical signs of sepsis were recruited as control group after informed consent. Vitamin D level (25 OH D) was assessed in the neonates and their mothers in both the groups. RESULTS:Neonatal 25 OH vitamin D level in the study group (12.71 ± 2.82 ng/ml) was significantly lower than in the control group (25.46 ± 7.02 ng/ml). The Odds ratio was 273 (95% CI 30.39-2451.6) for culture positive sepsis in neonates with vitamin D deficiency/insufficiency. Mothers of septic neonates had significantly lower 25 OH vitamin D level (20.92 ± 3.92 ng/ml) than the mothers of healthy neonates in control group (27.31 ± 6.83 ng/ml). The Odds ratio was 4.71 (95% CI 1.69-13.1) for culture positive sepsis in babies born to mothers with vitamin D deficiency/insufficiency. CONCLUSIONS:Neonates with vitamin D deficiency/insufficiency are at higher risk for developing sepsis than those with sufficient vitamin D levels. Lower vitamin D levels in mothers is also associated with increased risk of sepsis in the neonates. 10.1007/s12098-020-03188-0
    Translational research and biomarkers in neonatal sepsis. Delanghe Joris R,Speeckaert Marijn M Clinica chimica acta; international journal of clinical chemistry As neonatal sepsis is a severe condition, there is a call for reliable biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect sepsis at an early stage. A moderate diagnostic accuracy of other acute phase proteins has been demonstrated (serum amyloid A, procalcitonin, lipopolysaccharide binding protein, mannose binding lectin and hepcidin). In neonatal sepsis, changed chemokine/cytokine levels are observed before those of acute phase reactants. High IL-6, IL-8, IL-10 and TNF-α concentrations are detected in infected infants. Soluble interleukin-2 receptor has been used to identify bacteremia, whereas low plasma RANTES concentrations are characteristic for septicemia. Several cell adhesion molecules contribute to the pathogenesis of sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during sepsis, whereas high sTREM-1 values in early-onset neonatal sepsis (EOS) have been associated with mortality. Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic infection and/or inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered protein expression patterns. The ApoSAA score is useful for identifying sepsis and could guide prescription of antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose septic shock, which is associated with increased concentrations of 2-hydroxybutyrate, 2-hydroxyisovalerate, 2-methylglutarate, creatinine, glucose and lactate. 10.1016/j.cca.2015.01.031
    Screening for early onset neonatal sepsis: NICE guidance-based practice versus projected application of the Kaiser Permanente sepsis risk calculator in the UK population. Goel Nitin,Shrestha Sudeep,Smith Rhian,Mehta Akshay,Ketty Malini,Muxworthy Helen,Abelian Artur,Kirupaalar Vickness,Saeed Shakir,Jain Shikha,Asokkumar Amar,Natti Murali,Barnard Ian,Pitchaikani Prem Kumar,Banerjee Sujoy Archives of disease in childhood. Fetal and neonatal edition OBJECTIVE:To compare management recommendations of the National Institute for Health and Care Excellence (NICE) guidelines with the Kaiser Permanente sepsis risk calculator (SRC) for risk of early onset neonatal sepsis (EONS). DESIGN:Multicentre prospective observational projection study. SETTING:Eight maternity hospitals in Wales, UK. PATIENTS:All live births ≥34 weeks gestation over a 3-month period (February-April 2018). METHODS:Demographics, maternal and infant risk factors, infant's clinical status, antibiotic usage and blood culture results from first 72 hours of birth were collected. Infants were managed using NICE recommendations and decisions compared with that projected by SRC. MAIN OUTCOME MEASURE:Proportion of infants recommended for antibiotics on either tool. RESULTS:Of 4992 eligible infants, complete data were available for 3593 (71.9%). Of these, 576 (16%) were started on antibiotics as per NICE recommendations compared with 156 (4.3%) projected by the SRC, a relative reduction of 74%. Of the 426 infants avoiding antibiotics, SRC assigned 314 (54.6%) to normal care only. There were seven positive blood cultures-three infants were recommended antibiotics by both, three were not identified in the asymptomatic stage by either; one was a contaminant. No EONS-related readmission was reported. CONCLUSION:The judicious adoption of SRC in UK clinical practice for screening and management of EONS could potentially reduce interventions and antibiotic usage in three out of four term or near-term infants and promote earlier discharge from hospital in >50%. We did not identify any EONS case missed by SRC when compared with NICE. These results have significant implications for healthcare resources. 10.1136/archdischild-2018-316777
    Serum stromal-derived-factor-1 (CXCL12) and its alpha chemokine receptor (CXCR4) as biomarkers in neonatal sepsis. Badr Hassan S,El-Gendy Fady M,Helwa Mohamed A The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians BACKGROUND:Neonatal sepsis remains one of the leading causes of morbidity and mortality both among term and preterm infants. Advances in neonatal care improved survival and reduced complications in preterm infants. Chemokines are chemotactic cytokines that give directional guidance for leukocyte migration during inflammatory process. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in inflammatory states. However, its value as a biomarker in neonatal sepsis is unclear. OBJECTIVES:To assess the value of measuring the serum levels of alpha-chemokine receptor type 4 (CXCR-4) and stromal-derived-factor-1 (CXCL12) in diagnosis of late onset neonatal sepsis. SUBJECT AND METHODS:Serum levels of CXCL12 and CXCR4 were determined in 38 full term neonates, 23 cases of late onset sepsis (13 males and 10 female), and 15 healthy neonates as control (six males and nine females) by ELISA technique and flow-cytometry. RESULTS:Serum levels of CXCR4 and CXCL12 were significantly higher in neonates with late onset sepsis compared with the non-septic ones. The sensitivity, the specificity, and the overall accuracy of CXCL12 were 100%. The sensitivity of CXCR4 was 87%; the specificity was 80% and the overall accuracy was 84%. CONCLUSIONS:Serum CXCR4 and CXCL12 levels increase significantly in septic neonates and they are valuable marker in diagnosis of neonatal sepsis. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis. 10.1080/14767058.2017.1336760
    Clinical features and antimicrobial susceptibility profiles of culture-proven neonatal sepsis in a tertiary children's hospital, 2013 to 2017. Li Xiaoxia,Ding Xiangyu,Shi Peng,Zhu Yiqing,Huang Yidie,Li Qin,Lu Jinmiao,Li Zhiping,Zhu Lin Medicine Neonatal sepsis (NS) remains a major cause of morbidity and mortality in neonates, but data on the etiology and antibiotic susceptibility patterns of pathogens are limited. The aim of this study was to analyze the clinical characteristics, risk factors, and the antibiotic susceptibility patterns of pathogenic microbes associated with NS at a tertiary children's hospital in Shanghai, China.Episodes of blood culture-proven sepsis in the neonatal intensive care unit (NICU) of Children's Hospital of Fudan University from January 2013 to August 2017 were retrospectively reviewed. Collected data included demographics, perinatal risk factors, clinical symptoms, laboratory values, microbiology results and their antimicrobial susceptibility. Data for early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) were compared.The 341 of 976 culture-positive cases were selected, including 161 EONS cases (47.21% of 341) and 180 LONS cases (52.79% of 341). 635 incomplete cases were excluded. There was significant difference in risk factors between the EONS group and LONS group including birth weight, gestational age, 1-minute Apgar score, respiratory support, and the use of peripherally insertion central catheter (PICC). Clinical symptoms such as fever, feeding intolerance, abdominal distension, and neonatal jaundice, and laboratory results such as hemoglobin and lymphocyte counts also showed between-group differences. Staphylococcus epidermidis (22.87%), Escherichia coli (9.68%), Alcaligenes xylosoxidans (9.38%) and Klebsiella pneumoniae (9.09%) remain the principal organisms responsible for neonatal sepsis. Most isolates of Gram-positive bacteria were sensitive to vancomycin, linezolid, minocycline and tigecycline, of which more than 90% were resistant to penicillin. Most isolates of Gram-negative bacteria were sensitive to amikacin and imipenem and resistant to ampicillin. Fungus was sensitive to antifungal agents. Better medical decisions, especially early detection and appropriate initial antimicrobial therapy can be made after understanding the different clinical features and pathogens of EONS and LONS. 10.1097/MD.0000000000014686
    Clinical and microbiological profile of babies born with risk of neonatal sepsis. Zhou Bin,Liu Xiao,Wu Jie-Bin,Jin Bao,Zhang Yan-Yan Experimental and therapeutic medicine The aim of the present study was to evaluate the effects of antibiotics on the condition of babies born with risk of neonatal sepsis. From March, 2014 to February, 2015, 200 neonates born with risk factors of septicemia in the Neonatal Intensive Care Unit at Xuzhou Central Hospital, were enrolled in the present study. Venous blood samples were collected within 6 h of birth using aseptic technique. Part of the blood specimens were cultured using BACTEC PEDS PLUS/F Culture Vials. Subsequently, the subcultures were prepared from each presumptive positive vial and bacterial isolates were identified. The remaining portion was used to measure the level of C-reactive protein (CRP) and total leukocyte count (TLC). The result showed that 32% of neonates were infected, of whom, 21.9% had , 21.9% had , and 12.5% had . Additionally, , ., and was isolated from 9.4, 7.8, 6.3 and 4.7% of neonates, respectively. The neonates enrolled in the present study had ≥1 risk factor for neonatal sepsis, and the average number of risk factors was 1.95 per neonate. Neonates (39.1%) with positive blood culture results, had a CRP level >0.8 mg/dl, and 12.5% was shown to have an abnormal increase in their leukocyte counts. The association between leukocyte counts and blood culture results was not statistically significant. Of the neonates with positive blood cultures 45.3% died within 7 days after birth, while there was no mortality among those with negative culture results. The results indicate that in the presence of risk factors for sepsis, irrespective of clinical features of septicemia, neonatal sepsis screening should be performed. Rational and appropriate use of antibiotics may minimize the emergence of multidrug resistant bacteria in neonatal units. 10.3892/etm.2016.3836
    The Utility of Neutrophil CD64 and Presepsin as Diagnostic, Prognostic, and Monitoring Biomarkers in Neonatal Sepsis. Hashem Heba E,Abdel Halim Rania M,El Masry Sherin A,Mokhtar Amira M,Abdelaal Noureldin M International journal of microbiology Background:Neonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients. Aim:To evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs). Methods:235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group ( = 102) and the sepsis group ( = 133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) ( = 20) and (group 2: improved sepsis group) ( = 42). Results:Significant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686 pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 ( < 0.001) and hs-CRP (=0.018) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC value -5.904 for nCD64% followed by dC value -4.494 for presepsin. Conclusion:nCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis. 10.1155/2020/8814892
    Risk factors and etiology of neonatal sepsis after hospital delivery: A case-control study in a tertiary care hospital of Rajshahi, Bangladesh. Rafi Md Abdur,Miah M Morsed Zaman,Wadood Md Abdul,Hossain Md Golam PloS one BACKGROUND:Sepsis is one of the major causes of neonatal death worldwide as well as in Bangladesh. The objective of the present study was to identify the risk factors and causative organisms of neonatal sepsis after delivery in a tertiary care hospital, Bangladesh. METHODS:This was a case-control study conducted in the neonatal ward of Rajshahi Medical College Hospital (RMCH), a 1000-bed tertiary hospital situated in Rajshahi, Bangladesh. Neonates diagnosed as neonatal sepsis by clinical and laboratory parameters were included as cases in this study. Admitted neonates unsuspected or undiagnosed for sepsis were considered as controls. Maternal and neonatal information and their laboratory reports were collected and analyzed. Both bivariate and multiple logistic regression models were used to identify the risk factors of neonatal sepsis. RESULTS:A total of 91 cases and 193 controls were included in the study. Maternal history of urinary tract infection (UTI) during the third trimester of pregnancy (aOR 2.75, 95% CI: 1.04-7.23, p <0.05), premature birth (aOR 2.77, 95% CI: 1.08-7.13, p <0.05) and APGAR score <7 at five minutes (aOR 2.58, 95% CI: 1.04-6.39, p <0.05) were associated with onset of neonatal sepsis in multiple logistic regression model. All these factors were also associated with developing early-onset neonatal sepsis, while maternal UTI and male sex of neonates were associated with developing late-onset neonatal sepsis. Escherichia coli (40.7%), Staphylococcus aureus (27.5%), and Klebsiella pneumoniae (18.7%) were the commonly isolated organisms causing neonatal sepsis. All these organisms were highly resistant to common antibiotics like amoxicillin, cephalosporins, aminoglycosides and quinolones. Carbapenemase group of drugs along with amikacin, nitrofurantoin and linezolid were the most sensitive drugs. CONCLUSIONS:Strengthening the existing facility for antenatal screening for early diagnosis and treatment of maternal infection during pregnancy as well as identifying high-risk pregnancy for adequate perinatal management is necessary to prevent neonatal sepsis-related morbidity and mortality. Rational use of antibiotics according to local epidemiology and culture and sensitivity reports may minimize the increasing hazards of antibiotic resistance. 10.1371/journal.pone.0242275
    Neonatal sepsis: within and beyond China. Dong Ying,Basmaci Romain,Titomanlio Luigi,Sun Bo,Mercier Jean-Christophe Chinese medical journal Sepsis remains a significant cause of neonatal morbidity and mortality in China. A better understanding of neonatal sepsis in China as compared with other industrialized and non-industrialized countries may help optimize neonatal health care both regionally and globally. Literature cited in this review was retrieved from PubMed using the keywords "neonatal sepsis," "early-onset (EOS)" and "late-onset (LOS)" in English, with the focus set on population-based studies. This review provides an updated summary regarding the epidemiology, pathogen profile, infectious work-up, and empirical treatment of neonatal sepsis within and beyond China. The incidence of neonatal EOS and the proportion of Group B Streptococcus (GBS) within pathogens causing EOS in China seem to differ from those in developed countries, possibly due to different population characteristics and intrapartum/postnatal health care strategies. Whether to adopt GBS screening and intrapartum antibiotic prophylaxis in China remains highly debatable. The pathogen profile of LOS in China was shown to be similar to other countries. However, viruses as potential pathogens of neonatal LOS have been underappreciated. Growing antimicrobial resistance in China reflects limitations in adapting antibiotic regimen to local microbial profile and timely cessation of treatment in non-proven bacterial infections. This review stresses that the local epidemiology of neonatal sepsis should be closely monitored in each institution. A prompt and adequate infectious work-up is critically important in diagnosing neonatal sepsis. Adequate and appropriate antibiotic strategies must be overemphasized to prevent the emergence of multi-resistant bacteria in China. 10.1097/CM9.0000000000000935
    50 Years Ago in TheJournalofPediatrics: Neonatal Septicemia. Bedi Nidhi,Kumar Chandra Mohan,Gupta Piyush The Journal of pediatrics 10.1016/j.jpeds.2019.07.070
    Interleukin-6 and interleukin-8 in diagnosing neonatal septicemia. Wu Y Q,Shen J,Zhou Q L,Zhao H W,Liu L R,Liu X Journal of biological regulators and homeostatic agents Neonatal septicemia (NS) is a common cause of death of newborn infants, hence early diagnosis and treatment are of the utmost importance. However, lack of specific clinical symptoms and late detection delay a correct diagnosis. It is therefore of great importance to establish auxiliary indexes for the early diagnosis of NS. To evaluate the value of interleukin (IL-6 and IL-8) in the diagnosis of NS, a prospective study was carried out. Seventy-five newborns who developed septicemia and received treatment in our hospital from January 2013 to December 2014 were selected as research subjects; also, 50 healthy newborns were set as a control group. The levels of serum IL-6 and IL-8 were compared between the two groups. Results demonstrated that levels of C-reactive protein (CRP), IL-6 and IL-8 of the septicemia group were higher than those of the control group on admission, although the difference had no statistical significance (P less than 0.05); the septicemia group had higher sequential organ failure assessment (SOFA) scores but lower pediatric critical illness scores (PCIS) compared to the control group (P less than 0.05); levels of CRP, IL-6 and IL-8 were in positive correlation to the SOFA scores and in negative correlation to PCIS. Analysis of receiver operating characteristics (ROC) curve demonstrated that the sensitivity, specificity and accuracy were 85.7%, 80.2% and 81.8%, respectively, when IL-6 level was set as 32 pg/mL, 78.1%, 64.2% and 66.9%, respectively when IL-8 level was set as 54 pg/mL, and 71.4%, 86.3% and 82.7% respectively, when detection of IL-6 and IL-8 were combined together. Hence it can be concluded that: IL-6 and IL-8 are involved in inflammatory reactions; levels of IL-6 and IL-8 were correlated to the severity of the infection; the value of IL-6 is higher than that of IL-8 in the diagnosis of neonatal septicemia and the combined detection of IL-6 and IL-8 can improve the accuracy of the diagnosis of neonatal septicemia.
    The predictive value of joint detection of serum amyloid protein A, PCT, and Hs-CRP in the diagnosis and efficacy of neonatal septicemia. Wu F,Hou X-Q,Sun R-R,Cui X-J European review for medical and pharmacological sciences OBJECTIVE:This study aimed to investigate the predictive value of joint detection of serum amyloid A (SAA), plasma procalcitonin (PCT), and whole blood hypersensitive C-reactive protein (hs-CRP) in the diagnosis and efficacy of neonatal septicemia. PATIENTS AND METHODS:A total of 195 cases of neonatal septicemia patients admitted to our hospital from March 2013 to May 2017 were selected as observation group, and 100 healthy newborns in the same period were selected as control group. Before treatment, all newborns were detected with enzyme-linked immunosorbent assay (ELISA) for serum SAA, PCT, and hs-CRP three indicators respectively, and differences between expressions of PCT, HS-CRP, SAA in the serum of children (effective group) who improved after treatment and patients in ineffective group were observed. RESULTS:Three indexes of SAA, PCT, and hs-CRP in study group were significantly higher than those in control group before treatment, while three indexes of SAA, PCT, and hs-CRP in effective group were significantly lower than those in ineffective group after treatment, with statistical significance (p<0.05). By drawing the ROC curve, it was found that the AUC area, specificity, and sensitivity of joint detection were better than those of the single item detection. CONCLUSIONS:Joint detection of SAA, PCT, and hs-CRP has high diagnostic value in neonatal septicemia and is worthy of clinical application. 10.26355/eurrev_201907_18335
    Identification and antimicrobial resistance of pathogens in neonatal septicemia in China-A meta-analysis. Li Jing-Yang,Chen Shang-Qin,Yan Yan-Yan,Hu Ying-Ying,Wei Jia,Wu Qiu-Ping,Lin Zhen-Lang,Lin Jing International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases OBJECTIVES:The purpose of this study was to analyze the distribution and antimicrobial resistance of common bacterial pathogens causing neonatal septicemia based on a systematic review of published studies in China. METHODS:Articles on neonatal sepsis published in the Chinese literature from 2009 to 2014 were identified according to the inclusion and exclusion criteria. Data were extracted and analyzed using Comprehensive Meta-Analysis software. RESULTS:A total of 71 studies were included, in which a total of 8080 bacterial species were isolated from culture-positive blood samples. The pooled distribution rates of common bacterial pathogens were as follows: Staphylococcus 67.1% (95% confidence interval (CI) 63.3-70.6%), Enterococcus 4.1% (95% CI 3.5-4.8%), Streptococcus 2.3% (95% CI 1.6-3.2%), Escherichia coli 7.4% (95% CI 6.4-8.7%), Klebsiella 6.5% (95% CI 5.2-8.2%), Enterobacterium 2.3% (95% CI 1.9-2.8%), Acinetobacter 1.6% (95% CI 1.3-2.0%), Pseudomonas 1.7% (95% CI 1.3-2.2%). Among the Staphylococcus aureus strains isolated, more than 60% were methicillin-resistant (MRSA). In addition, over 50% of the Gram-negative isolates, including Escherichia and Klebsiella, were resistant to the commonly used third-generation cephalosporins. Most of the Gram-positive and Gram-negative bacteria isolated were sensitive to aminoglycosides, especially amikacin. CONCLUSIONS:It is concluded that Staphylococcus, especially coagulase-negative Staphylococcus, continues to be the principal organism responsible for neonatal septicemia in China; Enterobacteriaceae are common among the Gram-negative isolates. Significant numbers of MRSA and multidrug-resistant Gram-negative bacteria are being isolated as pathogens responsible for neonatal septicemia in China. 10.1016/j.ijid.2018.04.794
    Clinical Outcomes Related to the Gastrointestinal Trophic Effects of Erythropoietin in Preterm Neonates: A Systematic Review and Meta-Analysis. Ananthan Anitha,Balasubramanian Haribalakrishna,Rao Shripada,Patole Sanjay Advances in nutrition (Bethesda, Md.) Erythropoietin (EPO) plays an important role in the development and maturation of the gastrointestinal tract. Recombinant EPO (rEPO) has been used to prevent anemia of prematurity. The gastrointestinal trophic effects of EPO may reduce feeding intolerance and necrotizing enterocolitis (NEC) in preterm neonates. The aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the effects of rEPO on clinical outcomes such as feeding intolerance, stage II or higher NEC, any stage NEC, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia in preterm neonates. Twenty-five RCTs (intravenous: 13; subcutaneous: 10; enteral: 2; n = 4025) were eligible for inclusion. Meta-analysis of data from 17 RCTs (rEPO compared with placebo) with the use of a fixed-effects model showed no significant effect of rEPO on stage II or higher NEC (RR: 0.87; 95% CI: 0.64, 1.19; P = 0.39). Meta-analysis of data from 25 RCTs (rEPO compared with placebo) showed that rEPO significantly decreased the risk of any stage NEC [cases/total sample: 120/2058 (5.83%) compared with 146/1967 (7.42%); RR: 0.77; 95% CI: 0.61, 0.97; P = 0.03]. Only one RCT reported on time to full feedings. Meta-analysis of data from 15 RCTs showed a significant reduction in late-onset sepsis after rEPO administration (RR: 0.81; 95% CI: 0.71, 0.94; P = 0.004). Meta-analysis of 13 RCTs showed no significant effect of rEPO on mortality, retinopathy of prematurity, and bronchopulmonary dysplasia. Prophylactic rEPO had no effect on stage II or higher NEC, but it reduced any stage NEC, probably by reducing feeding intolerance, which is often labeled as stage I NEC. Adequately powered RCTs are required to confirm these findings. 10.1093/advances/nmy005
    Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis. Dulay Antonette T,Buhimschi Irina A,Zhao Guomao,Luo Guoyang,Abdel-Razeq Sonya,Cackovic Michael,Rosenberg Victor A,Pettker Christian M,Thung Stephen F,Bahtiyar Mert O,Bhandari Vineet,Buhimschi Catalin S American journal of obstetrics and gynecology OBJECTIVE:The objective of the study was to test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of nucleated red blood cells (NRBCs) independent of hypoxia or fetal stress. We sought to determine whether fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth. STUDY DESIGN:The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin (IL)-6, erythropoietin (EPO), cortisol, and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intraamniotic inflammation according to established parameters. NRBC counts were assessed within 1 hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO, and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics were used. RESULTS:Fetuses with EONS (n = 19) were delivered at earlier gestational ages (mean +/- SD: 27.1 +/- 2.8 weeks, P = .001) and more often by mothers with intraamniotic inflammation (P = .022) and histological chorioamnionitis (P < .001). Neonates with EONS had higher absolute NRBC counts (P = .011). NRBC counts were directly correlated with cord blood IL-6 levels (P < .001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction, and steroid exposure. CONCLUSION:In the setting of inflammation-associated preterm birth and in the absence of hypoxia, elevations in NRBCs in the early neonatal period may be a direct response of exposure to inflammatory mediators in utero. 10.1016/j.ajog.2008.01.040
    Implementation of the Neonatal Sepsis Calculator in Early-Onset Sepsis and Maternal Chorioamnionitis. Akangire Gangaram,Simpson Elizabeth,Weiner Julie,Noel-MacDonnell Janelle,Petrikin Joshua,Sheehan Michael Advances in neonatal care : official journal of the National Association of Neonatal Nurses BACKGROUND:Utilization of the neonatal sepsis calculator published by Kaiser Permanente is rapidly increasing. This freely available online tool can be used in assessment of early-onset sepsis (EOS) in newborns 34 weeks' gestation or more based on maternal risk factors and neonatal examination. However, many hospitals lack standard guidelines for its use, leading to provider discomfort with practice change. PURPOSE:The goal of this project was to study the antibiotic use rate for EOS at a level III neonatal intensive care unit and create standardized guidelines and staff education for using the sepsis calculator. Our ultimate goal was to decrease antibiotic use for EOS in newborns 34 weeks' gestation or more. METHODS:A standard quality improvement Plan-Do-Study-Act (PDSA) model was utilized with a plan to study the problem, implement the intervention, and test again for improvement. The primary outcome of interest was a decrease in the use of antibiotics for EOS in neonates 34 weeks' gestation or more. RESULTS:Over a 4-month period, prior to sepsis calculator implementation, antibiotic use for suspected EOS was 11% and blood culture was done on 14.8% of live births. After implementation of the sepsis calculator and completion of the PDSA cycle, sepsis calculator use was greater than 95%, antibiotic use dropped significantly to 5% (P = .00069), and blood culture use dropped to 7.6% (P = .00046). IMPLICATIONS FOR PRACTICE:Staff education and systematic intervention using a PDSA model can significantly impact patient care, decreasing the administration of antibiotics to infants at risk for sepsis. IMPLICATIONS FOR RESEARCH:Future research is needed to decrease antibiotic use in premature infants less than 34 weeks' gestation with similar risk factors and clinical features.Video Abstract available at https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=34&autoPlay=true. 10.1097/ANC.0000000000000668
    Risk Factors for Neonatal Sepsis: A Retrospective Case-Control Study among Neonates Who Were Delivered by Caesarean Section at the Trauma and Specialist Hospital, Winneba, Ghana. Adatara Peter,Afaya Agani,Salia Solomon Mohammed,Afaya Richard Adongo,Kuug Anthony K,Agbinku Ethel,Agyabeng-Fandoh Eric BioMed research international The third Sustainable Development Goal (SDG) for child health, which targets ending preventable deaths of neonates and children under five years of age by 2030, may not be met without substantial reduction of neonatal sepsis-specific mortality in developing countries. This study aimed at assessing the prevalence and risk factors for neonatal sepsis among neonates who were delivered via caesarean section. A retrospective case-control study was conducted among neonates who were delivered via caesarean section at the Trauma and Specialist Hospital, Winneba, Ghana. Data collection lasted for 4 weeks. The extracted data were double-entered using Epidata software version 3.1 to address discrepancies of data entry. Descriptive statistics such as frequencies and percentages of neonatal characteristics were generated from the data. Both univariate and multivariate logistic regression were used to determine associations between neonatal sepsis and neonatal characteristics with odds ratios, 95% confidence intervals, and p values calculated using variables that showed significant association (p<0.05) in the chi-square analysis for the multivariate logistic regression. A total of 383 neonates were recruited; 67 (17.5%) had sepsis (cases). The neonatal risk factors associated with sepsis were birth weight (2=6.64, p=0.036), neonatal age (2=38.31, p<0.001), meconium passed (2=12.95, p<0.001), reason for CS (2=24.27, p<0.001), and the duration of stay on admission (2=36.69, p<0.001). Neonatal sepsis poses a serious threat to the survival of the newborn as the current study uncovered 6.0% deaths among sepsis cases. The findings of this study highlight the need for routine assessment of neonates in order to identify risk factors for neonatal sepsis and to curb the disease burden on neonatal mortality. 10.1155/2018/6153501
    Potential biomarkers for effective screening of neonatal sepsis infections: An overview. Chauhan Nidhi,Tiwari Sukirti,Jain Utkarsh Microbial pathogenesis Neonatal sepsis, a clinical disorder developed by bacterial blood stream infections (BSI) in neonates, is one of the serious global public health problems that must be addressed. More than one million of the estimated global newborn deaths per year are occurred due to severe infections. The genesis of the infection is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS) of the disease. The clinical complications of neonatal sepsis may be associated with bronchopulmonary dysplasia, ductus arteriosus and necrotizing enterocolitis. The clinical diagnosis and treatment of neonatal sepsis is highly complicated. Over the past few years distinct biomarkers have been identified. Most widely used biomarkers are C-reactive protein, Procalcitonin (PCT) and Serum amyloid A (SAA). Until recently, many potential biomarkers including Cell Surface antigens and Bacterial surface antigens and genetic biomarkers are being investigated. Protein biomarkers, cytokines and chemokines are getting much interest for identification of neonatal sepsis infection. 10.1016/j.micpath.2017.03.042
    Serum Interleukin-33 as a Biomarker in Predicting Neonatal Sepsis in Premature Infants. Halil Halit,Tayman Cuneyt,Buyuktiryaki Mehmet,Okur Nilufer,Cakır Ufuk,Serkant Utku Combinatorial chemistry & high throughput screening BACKGROUND:Neonatal sepsis is considered as the most frequent cause of death in newborns. Early diagnosis is important to reduce mortality and morbidity. The rapid progression of the disease requires proper use of biomarkers specific for prompt diagnosis and intervention. OBJECTIVE:We aimed to evaluate the benefit of interleukin-33 serum levels in the diagnosis and treatment of neonatal sepsis. METHOD:We included 51 infants with neonatal sepsis as the main study group and 50 neonates without sepsis as the control group. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were measured on the 1st, 3rd and 7th days of sepsis in the study group and on the 3rd postpartum day in the control group, respectively. RESULTS:Serum levels of interleukin-6, interleukin-33 and C-reactive protein were significantly higher in the first day of sepsis. Serum levels of interleukin-6, interleukin-33 and C-reactive protein decreased significantly on the 3rd and the 7th days of antibiotic treatment. We found a significant relationship between interleukin-33 and C-reactive protein and between interleukin-6 and C-reactive protein on the first day of sepsis. CONCLUSION:Serum interleukin-33 level is up-regulated in neonatal sepsis, which might be used as a novel diagnostic marker and also a useful tool to predict prognosis in early neonatal sepsis. 10.2174/1386207321666180911090656
    Efficacy of cefotaxime combined with gamma globulins on C-reactive protein and procalcitonin in neonatal sepsis. Zhang Fan Cellular and molecular biology (Noisy-le-Grand, France) C-reactive protein (CRP) is encoded by CRP or PTX1 gene and procalcitonin (PCT) is produced by the CALC-1 gene induction. Both PCT and CRP are known as valued biomarkers markers in prediction of Serious Bacterial Infections (SBI) in children. This experiment carried out to analyze the efficacy of cefotaxime combined with gamma globulins on neonatal sepsis and the effect on CRP and PCT. For this purpose, a total of 120 sepsis children were selected and randomly divided into observation and control groups. Children in the control group were treated with cefotaxime, while children in the observation group were treated with cefotaxime combined with gamma globulins. The two groups were compared in terms of the relative measures of efficacy, the total effective rate of treatment, the incidence of complications and serum CRP and PCT levels before and after treatment. The clinical measures of the observation group were all lower than those of the control group, and the total effective rate of the treatment was higher than that of the control group, while the incidence of complications was lower than that of the control group. In addition, before treatment, there was no difference in CRP and PCT between the two groups; after treatment, the above measures in the observation group were lower than those in the control group. It is concluded that Cefotaxime combined with gamma globulins in the treatment of neonatal sepsis has significant efficacy and is clinically more effective than cefotaxime monotherapy. This combination can shorten clinical symptom remission time and hospital stay, improve serum CRP and PCT levels and promote the recovery of children, worthy of promotion.
    Diagnostic Role of CD64 on Different Immune Cells in Early Diagnosis of Neonatal Sepsis. Abdel-Aleem Noha F,Sorour Ashraf S,Elkholy Yasmine S,Sabry Amira M The Egyptian journal of immunology Neonatal sepsis is an important cause of morbidity and mortality among neonates. Early diagnosis leads to better prognosis. CD64 can be used as an early marker to detect neonatal sepsis with promising results. Advances in flow cytometry have made it possible to assess its level on different white blood cells rapidly, precisely and with minimal blood. The aim of the present work was to assess the role of CD64 expressed on neutrophils, monocytes and lymphocytes in establishing diagnosis of neonatal sepsis as well as to compare its diagnostic value with CRP in diagnosis of neonatal sepsis. This study was performed on 80 neonates divided into 60 cases of neonatal sepsis (48 case of clinical sepsis & 12 cases of lab confirmed sepsis) and 20 healthy control neonates. Cases and controls were subjected to history taking, clinical examination and lab investigations in the form of CBC, CRP, CD64 expression on neutrophils, monocytes & lymphocytes and Blood culture (for cases only). Our study showed that CD64 expression on WBCs increases significantly in neonates with neonatal sepsis (P < 0.05) in comparison to controls. Results also showed that neutrophils CD 64 is the most sensitive indicator for detection of sepsis (sensitivity=95%, NPV=78.57%) at a cut off value of 0.18%, whereas CRP has shown the best specificity at a cut off value 3mg/Ml (specificity= 85%). In conclusion, neutrophil CD64 is superior to monocyte and lymphocyte CD64 and serum CRP in diagnosis of neonatal sepsis.
    Cytokine profile as diagnostic and prognostic factor in neonatal sepsis. Leal Yelda A,Álvarez-Nemegyei José,Lavadores-May Ana I,Girón-Carrillo Jorge Luis,Cedillo-Rivera Roberto,Velazquez Juan R The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians The serum levels of some cytokines can be useful in the diagnosis of neonatal sepsis; the prognostic value of a cytokine profile has not, to our knowledge, been explored in this disease. The objective of this study is to evaluate the diagnostic value of the serum levels of cytokines IL-1, -2, -4, -5, -6, -7, -8, -10, -12, -13, and -17, TNF, IFNγ, G-CSF, GM-CSF, MCP1, and MIP1β in neonates with high risk of developing sepsis. Sepsis was evaluated in 96 high-risk neonates. We assessed cytokine levels on hospital admission and during or not during sepsis. Fifty (52%) presented sepsis (26 early and 24 late). Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF. IL-6 values of ≥40.1 pg/mL were associated with the development of any type of sepsis (relative risk [RR]: 1.70; 95% confidence interval [95% CI]: 1.18-2.24;  = .01), while IL-6 values of ≥44.9 pg/mL were associated with early sepsis (RR: 1.29; 95% CI: 1.29-4.56;  = .01). In neonates with high risk for the development of sepsis, there is an association between levels of IL-6, IL-10, and G-SCF and the disease development/outcome. 10.1080/14767058.2018.1449828
    Clinical Characteristic and Pathogen Spectrum of Neonatal Sepsis in Guangzhou City from June 2011 to June 2017. Guo Junfei,Luo Yasha,Wu Yongbing,Lai Weiming,Mu Xiaoping Medical science monitor : international medical journal of experimental and clinical research BACKGROUND Preterm and low birth weight (birth weight <2500 g) neonates are vulnerable to sepsis, and the causative pathogens vary in different regions and times. The objective of this study was to identify common organisms leading to neonatal sepsis and identify the characteristic of patients infected with different bacteria, which may help in the selection of antibiotics for empirical treatment. MATERIAL AND METHODS We retrospectively collected the clinical and microbiological data of neonates with culture-proven sepsis in our clinical setting from June 2011 to June 2017. The demography, composition, and distribution of the pathogens and the clinical characteristic of the cases infected with different bacteria were analyzed. RESULTS Of a total of 1048 bacteria that were isolated from patient samples, detailed clinical and microbiological data of 297 cases were available. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative Staphylococcus (co-NS) were the top 3 isolated pathogens. Streptococcus agalactiae predominantly led to early-onset sepsis, while K. pneumoniae and Staphylococcus aureus mainly led to late-onset sepsis. K. pneumoniae was mainly acquired in the hospital. Leukopenia was more commonly seen than leukocytosis in our study, and patients infected with K. pneumoniae and Candida spp encountered more thrombocytopenia. CONCLUSIONS The results of our study revealed the composition of the pathogens of neonatal sepsis in our region and the clinical characteristic of sepsis caused by different bacteria; these data may help in the selection of antibiotics for empirical treatment of neonates with high risk of sepsis. 10.12659/MSM.912375
    The diagnostic accuracy of presepsin in neonatal sepsis: a meta-analysis. Bellos Ioannis,Fitrou Georgia,Pergialiotis Vasilios,Thomakos Nikolaos,Perrea Despina N,Daskalakis Georgios European journal of pediatrics There is growing evidence that presepsin is a promising biomarker in the diagnosis of sepsis in adults. The objective of our study is to investigate current evidence related to the diagnostic accuracy of presepsin in neonatal sepsis. To accomplish this, we searched the Medline (1966-2017), Scopus (2004-2017), Clinicaltrials.gov (2008-2017), EMBASE (1980-2017), Cochrane Central Register of Controlled Trials CENTRAL (1999-2017), and Google Scholar (2004-2017) databases. Eleven studies were included in the present meta-analysis, with a total number of 783 neonates. The pooled sensitivity of serum presepsin for the prediction of neonatal sepsis was 0.91 (95% CI [0.87-0.93]) and the pooled specificity was 0.91 (95% CI [0.88-0.94]). The diagnostic odds ratio was 170.28 (95% CI [51.13-567.11]) and the area under the curve (AUC) was 0.9751 (SE 0.0117). Head-to-head comparison with AUC values of C-reactive protein (0.9748 vs. 0.8580) and procalcitonin (0.9596 vs. 0.7831) revealed that presepsin was more sensitive in detecting neonatal sepsis. CONCLUSION:Current evidence support the use of presepsin in the early neonatal period in high-risk populations as its diagnostic accuracy seems to be high in detecting neonatal sepsis. What is known: • Neonatal sepsis is a leading cause of morbidity and mortality. • Current laboratory tests cannot accurately discriminate endangered neonates. What is new: • The diagnostic odds ratio of presepsin is 170.28 and the area under the curve is 0.9751. • According to our meta-analysis, presepsin is a useful protein that may help clinicians identify neonates at risk. 10.1007/s00431-018-3114-1
    Diagnostic value of neutrophil CD64 combined with CRP for neonatal sepsis: A meta-analysis. Song Yan,Chen Yuanchun,Dong Xue,Jiang Xiaohua The American journal of emergency medicine BACKGROUND:Sepsis is the leading cause of morbidity and mortality in newborns. CD64 combined with c-reactive protein (CRP) could improve the sensitivity and specificity of neonatal sepsis diagnosis, but the results were still controversial. Therefore, this meta-analysis was conducted to clarify the importance of CD64 combined with CRP in the diagnosis of neonatal sepsis. METHODS:The researches published as of December 24, 2018 were comprehensively searched in PubMed, Embase (included Embase and Medline), the Cochrane Library and Web of Science. Totally, 8 articles were included, involving 1114 objects. Statistical calculations were performed using Stata14.0 and Review Manager 5.3. RESULTS:The diagnostic accuracy of all included studies was pooled as follows: sensitivity, 0.95 (95% CI: 0.86-0.98); specificity, 0.86 (95% CI: 0.74-0.93); positive likelihood ratio (PLR), 6.8 (95% CI: 3.50-13.20); negative likelihood ratio (NLR), 0.06 (95% CI: 0.02-0.18); diagnostic odds ratio (DOR), 118.0 (95% CI: 25.00-549.00), and the area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). It was found that heterogeneity was not caused by threshold effect (P = 0.16), but the results of sensitivity (I = 87.57%) and specificity (I = 89.07%) analyses indicated significant heterogeneity between studies. CONCLUSIONS:The combined application of CD64 and CRP improved the accuracy of neonatal sepsis diagnosis. 10.1016/j.ajem.2019.05.001
    Interleukin-6 for early diagnosis of neonatal sepsis with premature rupture of the membranes: A meta-analysis. Qiu Xia,Zhang Li,Tong Yu,Qu Yi,Wang Huiqing,Mu Dezhi Medicine BACKGROUND:Premature rupture of the membranes (PROM) is the principal risk factor for neonatal sepsis. Interleukin-6 (IL-6) has been investigated for early diagnosis of neonatal sepsis, but not for diagnosis of neonatal sepsis with PROM. The objective of this study is to investigate the early diagnostic value of IL-6 for neonatal sepsis with PROM. METHODS:The literature was searched using PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, VIP, and CBM databases until March 2018. Each study was evaluated using Quality Assessment of Diagnostic Accuracy Studies tool-2. We used a bivariate diagnostic random-effects model. RESULTS:The overall pooled sensitivity, specificity, positive likelihood rate, negative likelihood rate, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.85 (95% confidence interval [CI]: 0.81-0.91), 0.88 (95% CI: 0.86-0.91), 9.94 (95% CI: 4.27-23.15), 0.14 (95% CI: 0.06-0.32), 79.26 (95% CI: 23.42-268.26), and 0.9473, respectively, which showed high accuracy in diagnosing neonatal sepsis with PROM. The types of sepsis might be connected with the source of heterogeneity (P = .0351). CONCLUSION:IL-6 is therefore a sensitive and specific diagnostic marker for the early diagnosis of neonatal sepsis with PROM. 10.1097/MD.0000000000013146
    Serum Level of Antithrombin III (ATIII) Could Serve as a Prognostic Biomarker in Neonatal Sepsis. Samra Nashwa,AlGhwass Mohammed,Elgawhary Somaya,Hassan Mohammed,Bekhit Osama,Mohamed Wael,Eid Mohammed Fetal and pediatric pathology : Neonatal sepsis syndrome continues to have a high morbidity and mortality rate despite the progress in neonatal intensive care. There is no single diagnostic test which can reliably diagnose sepsis in the newborn, beside blood culture. Antithrombin III may be one promising single marker for sepsis syndrome diagnosis and prognosis. : We quantitated antithrombin III (ATIII) in neonates with sepsis syndrome and compared these levels to healthy controls. : ATIII levels were significantly lower in sepsis syndrome neonates (23.05 ± 3.66) compared to controls (35.50 ± 2.50), ( < 0.001). ROC curve for ATIII displayed area under the curve of 0.973, cutoff >30 mg/dL, a positive predictive value 90.47 and negative predictive value 96.55. : Antithrombin III is lower in sepsis syndrome neonates and may be a useful biomarker in neonatal sepsis. 10.1080/15513815.2019.1587118
    Performance of Haematological Parameters in Early Diagnosis of Clinically Suspected Neonatal Sepsis. Nabi S N,Basak A K,Kamruzzaman M,Pervez A F,Musharraf M,Sultana N,Moniruzzaman A M,Majumder B K,Mostakim M A Mymensingh medical journal : MMJ Neonatal sepsis is one of the major health problems throughout the world and major cause of morbidity and mortality in developing countries. Positive blood culture considers the gold standard for confirmation of neonatal sepsis, but it does not provide rapid diagnosis. So this study was designed to find out the performance of haematological parameters in early diagnosis of neonatal sepsis. The objective of the study was to evaluate the performance of haematological parameters individually and in combination in early diagnosis of neonatal sepsis. It was a cross-sectional study conducted at neonatal ward, SCANU and obstetric ward of Rangpur Medical College Hospital from January 2014 to December 2015. A total of 70 neonates clinically suspected to have features of sepsis were included in this study. Another 70 healthy term neonates were included in the study as reference group. Blood sample were obtained to estimate TLC, ANC, immature neutrophil count, degenerative changes in PMNs, platelet count, I/T and I/M ratio. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the individual test and tests combination were calculated. Among the haematological parameters, performance of combined tests had high sensitivity, specificity, with PPV and NPV. Among the individual tests I/T and I/M ratio had high sensitivity (95%), specificity (85%, 90%), PPV (90%, 75%) and NPV (90%). There were 22 out of 70 neonates (31.42%) who had culture proven sepsis. Among 22 culture proven sepsis most commonly found organism were Escherichia Coli 12(54.5%) followed by Klebsiella 3(13.63%), Proteus 3(13.63%), Staphylococcus aureus 2(9.9%) and Salmonella 2(9.9%). There is no ideal test for diagnosis of early diagnosis of neonatal sepsis haematological parameters is useful adjunct test in identifying clinically suspected neonatal sepsis.
    Evaluate the diagnosis of neonatal sepsis by measuring interleukins: A systematic review. Boskabadi Hassan,Zakerihamidi Maryam Pediatrics and neonatology Neonatal sepsis is a dangerous and common disease among infants which is associated with high morbidity and mortality. Interleukins may be helpful for diagnosis of neonatal sepsis. Therefore, this study is conducted to investigate the role of interleukins in the diagnosis of neonatal sepsis. In this study, databases including PubMed, Cochrane Library, ISI and Google Scholar were searched up to 2016. Keywords were: Sepsis, neonatal, interleukins, prediction and diagnosis. Study inclusion criteria were: Articles about the relationship between the diagnosis of neonatal sepsis and interleukins; studies on babies; English and Persian articles and enough information from test results. Articles that had focused on adult sepsis or had used other markers except ILs or just their abstracts were available were excluded from the study. Of 100 searched studies, eventually, 16 articles were considered including 12 prospective studies, 3 cross-sectional studies and 1 retrospective study. IL6 has been studied more than other interleukins (50% of articles). ILs 6, 8 and 10 are among the initial markers of neonatal sepsis diagnosis. IL6 above 68 pg/ml had 85% sensitivity and 80% specificity, IL8 above 269.51 pg/ml had 80% sensitivity and 50% specificity, IL10 above 27 pg/ml had 60% sensitivity and 87% specificity and combined interleukins above 186.83 pg/ml had 75.63% sensitivity and 71.49% specificity in sepsis diagnosis. Interleukins can be helpful in the diagnosis of neonatal sepsis based on the results of this study. IL6 had the most sensitivity and IL10 had the most specificity for diagnosis of sepsis. 10.1016/j.pedneo.2017.10.004
    The combination of procalcitonin and C-reactive protein or presepsin alone improves the accuracy of diagnosis of neonatal sepsis: a meta-analysis and systematic review. Ruan Lin,Chen Guan-Yu,Liu Zhen,Zhao Yun,Xu Guang-Yu,Li Shu-Fang,Li Chun-Ni,Chen Lin-Shan,Tao Zheng Critical care (London, England) BACKGROUND:Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. METHOD:Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses. RESULTS:A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity. CONCLUSIONS:The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings. 10.1186/s13054-018-2236-1
    The value of delta neutrophil index in neonatal sepsis diagnosis, follow-up and mortality prediction. Celik Istemi Han,Arifoglu Ilter,Arslan Zehra,Aksu Gonul,Bas Ahmet Yagmur,Demirel Nihal Early human development BACKGROUND:The complete blood cell count (CBC) and peripheral blood smear were the most commonly ordered tests for the diagnosis of neonatal sepsis. Delta neutrophil index (DNI) shows leucocyte differentiation and calculated while CBC is performed. AIMS:We aimed to evaluate the value of DNI in neonatal sepsis. STUDY DESIGN:DNI was measured with Siemens Advia 2120 and 2120i devices. DNI was calculated as (neutrophil and eosinophil count in myeloperoxidase channel)-(polymorphonuclear leucocyte count in nuclear lobularity channel). RESULTS:Study population included 141 and 87 neonates in sepsis (110 proven, 31 clinical) and control groups. Demographic characters were similar between groups. Proven sepsis group had lower birthweight and higher late-onset sepsis rate than clinical sepsis and control groups. Median DNI (16.3 vs 1,4) and CRP (6.8 vs 0,03 mg/dl) were significantly higher in sepsis group. Proven sepsis group had significantly higher DNI level than clinical sepsis group (20.8 vs 9.1). Cut-off level of DNI was 4.6 with 85% sensitivity and 80% specificity. Cut-off level of CRP was 0.58 mg/dl with 81% sensitivity and 82% specificity. Combination of DNI and CRP gave 98% sensitivity and 76% specificity. Mortality rate in sepsis group was 39%. Median DNI level in patients with mortality was significantly higher (30.1 vs 9.6). Cut-off level of DNI for mortality prediction was 16.1 with 75% sensitivity and 65% specificity. Follow-up levels of DNI was significantly decreased in 6-10 days to normal levels (16.3 to 4.2). CONCLUSIONS:DNI was found to be useful in the diagnose, follow-up and mortality prediction of neonatal sepsis without extra blood to CBC. 10.1016/j.earlhumdev.2019.02.003
    Accuracy of presepsin in neonatal sepsis: systematic review and meta-analysis. Parri Niccolò,Trippella Giulia,Lisi Catiuscia,De Martino Maurizio,Galli Luisa,Chiappini Elena Expert review of anti-infective therapy INTRODUCTION:Neonatal sepsis represents a major cause of morbidity and mortality in neonates. No diagnostic test has been demonstrated to be sufficiently accurate to confirm or exclude neonatal sepsis. This study aimed to evaluate the diagnostic accuracy of presepsin (P-SEP) for neonatal sepsis. Areas covered: A systematic review of literature was performed on Medline and EMBASE. A meta-analysis was performed to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic of P-SEP for neonatal sepsis. Eight studies were included, involving 636 neonates. Pooled sensitivity and specificity were 0.90 and 0.90, respectively. The pooled DOR was 120.94, and the Area Under Curve (AUC) was 0.968, indicating a high level of diagnostic accuracy. Using cut-off values <600 ng/L, sensitivity reached 0.93, with a specificity of 0.81 and AUC 0.8195, while using a threshold >600 ng/L, sensitivity was 0.87 and specificity 0.97, with higher diagnostic accuracy (AUC 0.976). Significant heterogeneity was found between studies. Expert commentary: Diagnostic accuracy of P-SEP resulted high in detecting neonatal sepsis. Even though it cannot be recommended as a single diagnostic test, P-SEP could be a helpful and valuable biomarker in neonates with suspected sepsis. 10.1080/14787210.2019.1584037
    Predictors of early-onset neonatal sepsis or death among newborns born at <32 weeks of gestation. Palatnik Anna,Liu Lilly Y,Lee Andy,Yee Lynn M Journal of perinatology : official journal of the California Perinatal Association OBJECTIVE:To develop a predictive model for early-onset neonatal sepsis or death among infants born at less than 32 weeks of gestation. STUDY DESIGN:This was a case-control study of all deliveries <32 weeks between 2011 and 2015 in a single tertiary care center. Cases were defined as neonates diagnosed with early-onset sepsis based on a blood or cerebrospinal fluid culture or neonates who expired during the first week of life. Controls consisted of neonates without these outcomes. Variables previously identified to be associated with neonatal sepsis or death were abstracted from the medical record. Bivariable analyses and multivariable logistic regression were used to determine independent risk factors for early-onset neonatal sepsis or death. An ROC curve was created and AUC calculated to estimate the predictive capacity of these associations. RESULTS:Of 779 eligible neonates, early-onset neonatal sepsis or death occurred in 73 (9.4%). In bivariable analyses, mothers whose neonates were diagnosed with early-onset sepsis or death were more likely to be obese, have an intrapartum fever, and have meconium-stained amniotic fluid, and were less likely to have received betamethasone or antepartum/intrapartum antibiotics. Gestational age at delivery and birth weight was significantly lower among neonates diagnosed with neonatal sepsis or death. In multivariable analyses, factors remaining independently associated with neonatal sepsis or death were earlier gestational age at the time of delivery (specifically <28 weeks), intrapartum fever, presence of meconium-stained amniotic fluid, and lower birth weight. The AUC for this regression was 0.81 (95% confidence interval 0.77-0.83). CONCLUSION:Earlier gestational age at the time of delivery, intrapartum fever, meconium, and lower birth weight are independently associated with early-onset neonatal sepsis or death among deliveries occurring at <32 weeks of gestation; these factors can be used to create a model with fair predictive capability. 10.1038/s41372-019-0395-9
    Neonatal Sepsis: Treatment of Neonatal Sepsis in Multidrug-Resistant (MDR) Infections: Part 2. Dudeja Sankalp Indian journal of pediatrics Sepsis is one of the major causes of neonatal deaths in India and worldwide. Pathogens encountered in neonatal sepsis vary worldwide; reports from developing countries more commonly show Gram negative organisms, most common being Acinetobacter spp., Klebsiella spp. and Escherichia coli. Recent studies show that the incidence of antimicrobial resistance, to third generation cephalosporins and carbapenems, has been on a rise. Because of widespread antimicrobial resistance, 'Higher' or 'Reserve' antibiotics are increasingly being used as first/second line antibiotics. In the past decade, there has been a resurgence in the use of colistin as a result of Extended-spectrum β-lactamase (ESBL)- producing Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE), which retain susceptibility only to colistin. The increasing burden of drug resistant Gram negative organisms, particularly Acinetobacter spp., Klebsiella spp., and E. coli might pose a formidable threat in coming years. 10.1007/s12098-019-03152-7
    C-reactive Protein as a Screening Biomarker in Neonatal Sepsis. Khan Faisal Journal of the College of Physicians and Surgeons--Pakistan : JCPSP OBJECTIVE:To measure validity of C-reactive protein (CRP) as screening test for neonatal sepsis (NS) and compare its screening validity between early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS). STUDY DESIGN:Cross-sectional study Place and Duration of Study: Neonatal Unit, Town Children Hospital, Peshawar, Khyber Pukhtunkhawa, from August 2016 to February 2017. METHODOLOGY:A total of 385 neonates from age 0 to 28 days with clinical features of neonatal sepsis were sampled using consecutive sampling technique. Two groups were identified, i.e. early onset neonatal sepsis (age <72 hours) and late onset neonatal sepsis (age >72 hours). Each neonate was sampled for blood culture and C-reactive protein (CRP). Diagnosis of neonatal sepsis was established through a positive blood culture. Data was analysed using SPSS V 25.0. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of CRP was measured and compared in each group. RESULTS:Analysis showed a low validity of CRP as screening test in neonatal sepsis (Sensitivity=35.525%, specificity=58.0%, PPV=85% and NPV=11.83%). Initial screening test validity of CRP was low in EONS (sensitivity=17.16%, specificity=58.33%, PPV=72.72% and NPV=9.81%) compared to LONS (sensitivity=77.45%, specificity=57.14%, PPV=92.94% and NPV=25.80) Conclusion: CRP as a screening test has low screening validity in early onset neonatal sepsis compared to late onset sepsis. 10.29271/jcpsp.2019.10.951
    Validity of biomarkers in screening for neonatal sepsis - A single center -hospital based study. Rashwan Nagwan I,Hassan Mohammed H,Mohey El-Deen Zeinab M,Ahmed Ahmed El-Abd Pediatrics and neonatology BACKGROUND:The diagnosis of neonatal sepsis still considered to be a challenge for both clinicians and the laboratory due to the non-specific clinical presentations. The present study aimed to compare and assess the diagnostic & prognostic values of C-reactive protein (CRP), high sensitivity CRP (hsCRP), presepsin, interleukin-6 (IL-6) and procalcitonin (PCT) in neonatal sepsis separately and in combination. METHODS:This hospital-based cross-sectional study has been conducted on 168 neonates recruited from the neonatal intensive care unit (NICU) of Qena University Hospitals, Upper Egypt. Measurements of CRP using latex agglutination test, hsCRP, presepsin, IL6 and PCT assays using commercially available ELISA assay kits were done to all included neonates. RESULTS:There were significantly higher serum levels of CRP among late onset versus early onset sepsis group with significantly higher serum levels of hsCRP and presepsin among early onset compared with the late onset sepsis group (p < 0.05 for all). There were significantly higher hsCRP, presepsin and PCT serum levels in proven versus probable sepsis group (p < 0.05 for all). Significantly higher serum levels of presepsin and PCT were noted among survivors versus non survivors sepsis group (p < 0.05 for all). The cutoff value of the serum level of CRP >6 mg/dl showed lower sensitivity and specificity than that of hsCRP at cutoff >140 ng/ml in diagnosing neonatal sepsis. The cutoff value of presepsin >200 ng/ml showed equal sensitivity and specificity to IL-6 at cutoff >22 pg/ml. The cutoff value of PCT at > 389 pg/ml showed sensitivity and specificity approximate to that of hsCRP. CONCLUSIONS:CRP could be a helpful prognostic marker in late onset neonatal sepsis. hsCRP and PCT have higher diagnostic accuracy in neonatal sepsis in comparison to other studied markers. Both IL-6 and presepsin have equal diagnostic utility in neonatal sepsis, but presepsin could be helpful diagnostic marker in early onset neonatal sepsis. 10.1016/j.pedneo.2018.05.001
    A meta-analysis of interleukin-6 as a valid and accurate index in diagnosing early neonatal sepsis. Sun Bo,Liang Lian-Fang,Li Jie,Yang Dan,Zhao Xiao-Bing,Zhang Ke-Gang International wound journal We aimed to systematically assess the overall value of interleukin 6 (IL-6) in diagnosing neonates with sepsis. A systematic literature search was conducted using the following electronic databases: PubMed, Embase, and Cochrane, to identify eligible studies through the index words updated till November 2018. Cross-sectional studies, as well as prospective cohort studies, were included in the above-mentioned group of eligible studies. We also searched the literature sources that had a link to the present study, which were further assessed by heterogeneity through the use of a proper-effects model to calculate pooled weighted specificity, sensitivity, and diagnostic odds ratio (DOR). We also conducted summary receiver operating characteristic (SROC) analyses for neonatal sepsis. In the present meta-analysis, there were 31 studies exploring IL-6 for the diagnostic accuracy of neonatal sepsis. The global specificity and sensitivity of IL-6 for neonatal sepsis were as follows: 88% (95% confidence interval [CI]: 83%-92%) and 82% (95% CI: 77%-86%), respectively. The global positive and negative likelihood ratio of IL-6 in diagnosing neonatal sepsis were 7.03 (95% CI: 4.81-10.26) and 0.20 (95% CI: 0.15-0.26), respectively. The global DOR was 29.54 (95%CI: 18.56-47.04) of IL-6. In addition, the area under the SROC was high for IL-6 (AUC = 0.92; 95% CI: 0.89-0.94). In this study, we performed a systematic review and meta-analysis to assess the diagnostic accuracy studies of IL-6 in diagnosing neonatal sepsis. Our results suggested that IL-6 is a valid and accurate index in diagnosing early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations. 10.1111/iwj.13079
    Efficacy of zinc supplementation for neonatal sepsis: a systematic review and meta-analysis. Tang Zhijun,Wei Zonghui,Wen Fei,Wu Yongdei The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Zinc supplementation has some potential in treating neonatal sepsis. We conduct a systematic review and meta-analysis to explore the efficacy of zinc supplementation for neonatal sepsis. PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases are systematically searched. Randomized controlled trials (RCTs) assessing the efficacy of zinc supplementation in neonatal sepsis are included. Two investigators independently search articles, extract the data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. Four RCTs involving 986 patients are included in the meta-analysis. Overall, compared with control intervention in neonatal sepsis, zinc supplementation is able to significantly reduce mortality rate (risk ratio (RR) = 0.48; 95% confidence intervals (CIs) = 0.25-0.94;  = .03) and improve serum zinc (mean difference (MD) = 81.97; 95% CI = 34.57-129.37;  = .0007), but has no remarkable influence on hospital stay (MD = -4.51; 95% CI = -15.08 to 6.05;  = .40) and the number of expired patients (RR = 0.63; 95% CI = 0.24-1.65;  = .35). Zinc supplementation may significantly reduce mortality rate and improve serum zinc in neonatal sepsis, but has no substantial influence on hospital stay and the number of expired patients. 10.1080/14767058.2017.1402001
    Red cell distribution width and its association with mortality in neonatal sepsis. Martin Snehal L,Desai Saumil,Nanavati Ruchi,Colah Roshan B,Ghosh Kanjaksha,Mukherjee Malay B The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians OBJECTIVE:Neonatal sepsis is a major cause of mortality in the developing countries. However, with current severity scores and laboratory parameters, predicting outcomes of neonatal sepsis is a serious challenge. Red cell distribution width (RDW) is a readily available pragmatic means to predict outcomes of various comorbidities in adults and children, without causing any additional blood loss. However, its utility in neonates remains unexplored. Hence, the objective of the present study was to evaluate the association of RDW with neonatal sepsis and its role as a predictive marker for mortality. METHODS:This Prospective observational study was carried out in a Level IIIB NICU for a period of 3 years. It involved comparison of RDW values of septic neonates with those of controls (matched for gestational age and birth weight) with an equal allocation ratio. A total of 251 septic neonates along with 251 controls >28 weeks of gestational age were enrolled. The RDW was derived from complete blood count done within first 6 hours of life. After arranging the RDW (median; interquartile range (IQR)), the values were categorized as those above the 50th percentile i.e. ≥20% and those below the 50th percentile i.e. <20%. The cumulative survival rates of the above two groups were assessed using the Kaplan-Meier curve and the log rank test. RESULTS:RDW levels were significantly higher among the neonatal sepsis cases (19.90%) as compared to the controls (18.90%) with a p value of < .001. RDW was significantly higher amongst the nonsurvivors than survivors (p < .003). Kaplan-Meier curve showed that septic neonates having RDW values ≥20% had significantly increased mortality (p < .02) with a hazard ratio of 0.5. CONCLUSIONS:High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis. 10.1080/14767058.2017.1421932
    Comparison between presepsin and procalcitonin in early diagnosis of neonatal sepsis. Iskandar Agustin,Arthamin Maimun Z,Indriana Kristin,Anshory Muhammad,Hur Mina,Di Somma Salvatore, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Neonatal sepsis remains worldwide one of the leading causes of morbidity and mortality in both term and preterm infants. Lower mortality rates are related to timely diagnostic evaluation and prompt initiation of empiric antibiotic therapy. Blood culture, as gold standard examination for sepsis, has several limitations for early diagnosis, so that sepsis biomarkers could play an important role in this regard. This study was aimed to compare the value of the two biomarkers presepsin and procalcitonin in early diagnosis of neonatal sepsis. This was a prospective cross-sectional study performed in Saiful Anwar General Hospital Malang, Indonesia, in 51 neonates that fulfill the criteria of systemic inflammatory response syndrome (SIRS) with blood culture as diagnostic gold standard for sepsis. At reviewer operating characteristic (ROC) curve analyses, using a presepsin cutoff of 706.5 pg/mL, the obtained area under the curve (AUCs) were sensitivity = 85.7%, specificity = 68.8%, positive predictive value = 85.7%, negative predictive value = 68.8%, positive likelihood ratio = 2.75, negative likelihood ratio = 0.21, and accuracy = 80.4%. On the other hand, with a procalcitonin cutoff value of 161.33 pg/mL the obtained AUCs showed: sensitivity = 68.6%, specificity = 62.5%, positive predictive value = 80%, negative predictive value = 47.6%, positive likelihood ratio = 1.83, the odds ratio negative = 0.5, and accuracy = 66.7%. In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide better early diagnostic value with consequent possible faster therapeutical decision making and possible positive impact on outcome of neonates. 10.1080/14767058.2018.1475643
    Study of Risk Factors, Causative Organisms & Their Sensitivity Pattern in Neonatal Sepsis in a Community Based Tertiary Level Hospital. Quddus A R,Islam M N,Uddin M B,Mahmud A A,Badruzzaman M,Saha S K,Sattar S,Afreen K F Mymensingh medical journal : MMJ Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. It is also a major cause of mortality in both developed and developing countries. The type and pattern of organisms that cause neonatal sepsis changes over time and vary from one hospital to another hospital, even in the same country. In addition the causative organisms have developed increased drug resistance for the last two decades. Maternal, neonatal and environmental risk factors have contributed for the development of sepsis. To study the risk factors, causative organism and bacterial sensitivity pattern in cases of neonatal sepsis. This cross-sectional study was conducted over a period of six months. The study included 100 patients admitted at the neonatal ward of Department of Pediatrics, Community Based Medical College Bangladesh, Mymensingh, Bangladesh. Blood samples for culture were taken aseptically before starting antibiotic therapy. Microorganisms were isolated and identified by standard microbiological processes and antimicrobial sensitivity patterns were performed against amikacin, gentamicin, ceftriaxone, ciprofloxacin and ceftazidime. The factors which carried a significant risk for development of neonatal sepsis were low birth weight, preterm neonates, meconium stained liquor and prolonged rupture of membrane (>18 hours). Gram negative organisms predominated (68.8%) with Escherichia coli (33.3%) being the commonest. The gram negative bacteria which were isolated sensitive to amikacin, gentamicin and ceftriaxone. The organisms also relatively more sensitive to ciprofloxacin and highly sensitive to ceftazidime. The Gram positive bacteria showed sensitivity against only the antibiotic Ceftriaxone and Ciprofloxacin. The overall mortality was 9%. The outcome of the study will contribute to preventing and treating neonatal sepsis in the hospital.
    Predictors of mortality in outborns with neonatal sepsis: A prospective observational study. Meshram Rajkumar Motiram,Gajimwar Vishal S,Bhongade Swapnil D The Nigerian postgraduate medical journal Background:Neonatal sepsis-related mortalities are the outcome of a complex interaction of maternal-foetal colonisation, transplacental immunity and physical and cellular defence mechanisms of neonates. Objective:The objective of this study was to evaluate the risk factors of mortality in outborn neonatal sepsis. Materials and Methods:A 1-year prospective observational study was undertaken at a tertiary care centre. All referred neonates with maternal and neonatal risk factors of sepsis were enrolled. Blood culture, sepsis screen and other relevant investigations were performed. Results:The mortality rate of neonatal sepsis among outborns was 38.24%. The common presentations of these neonates were respiratory distress, lethargy and hypothermia. On univariate analysis, significant risk factors for mortality included male sex (P = 0.05), weight on admission <1500 g (P < 0.001), hypothermia (P = 0.003), respiratory distress (P = 0.04), cyanosis (P = 0.001), convulsions (P = 0.02), prolonged capillary refill time (P < 0.001), thrombocytopenia (P < 0.001), abnormal radiological finding (P = 0.01), cerebrospinal fluid cellularity (P = 0.002) and positive C-reactive protein (P < 0.001). Maternal factors such as hypertension in pregnancy (P = 0.001) and antepartum haemorrhage (P = 0.03) were associated with statistically significant mortality. Gestational age (odds ratio [OR]: 0.49, confidence interval [CI]: 0.26-0.90, P = 0.02), weight on admission (OR: 1.57, CI: 1.08-2.27, P = 0.01), age at admission (OR: 0.89, CI: 0.78-0.99, P = 0.04), distance travelled with neonate (OR: 1.01, CI: 1.00-1.01, P = 0.003), duration of hospital stay (OR: 0.69, CI: 0.63-0.74, P < 0.001), hypothermia (OR: 1.87, CI: 1.01-3.42, P = 0.04), convulsion (OR: 2.88, CI: 1.33-6.20, P = 0.007), cyanosis (OR: 2.39, CI: 1.07-5.35, P = 0.03) and prolonged capillary refill time (OR: 3.34, CI: 1.78-6.24, P < 0.001) were the independent predictors of mortality in neonatal sepsis. Conclusion:Gestational age; birth weight; long distance travelled with neonate and presentation with hypothermia, cyanosis, convulsions and prolonged capillary refill time were the independent risk factors for mortality in neonatal sepsis among outborns. 10.4103/npmj.npmj_91_19
    Diagnostic value of mean platelet volume for neonatal sepsis: A systematic review and meta-analysis. Wang Jingjing,Wang Zhen,Zhang Min,Lou Zhenshuai,Deng Jiaxiang,Li Qian Medicine BACKGROUND:An increasing number of studies in recent years have identified mean platelet volume (MPV) as a predictive marker for neonatal sepsis. However, most of these studies focused on single regions, and therefore, the findings remain inconclusive. We, in this study, aimed to evaluate the potential of MPV as a biological indicator of neonatal sepsis through a systematic review and meta-analysis. METHODS:We searched PubMed, the Cochrane Library, Embase, and WanFang database for articles on MPV and neonatal sepsis, published from January 1, 1990 to December 31, 2018. We included 11 studies on 932 neonates with sepsis in this meta-analysis. RESULTS:The overall meta-analysis showed that MPV was significantly higher in patients with neonatal sepsis compared with healthy controls. Subgroup analysis revealed that the type of diagnostic criteria, analyzer, analyte, and controls used in the studies affected the difference in MPV between patients and healthy controls. CONCLUSION:MPV was significantly higher in the neonatal sepsis group compared to the control group. Therefore, in clinical practice, MPV could be used as an indicator for the early diagnosis of neonatal sepsis. 10.1097/MD.0000000000021649
    The challenges of neonatal sepsis management. Procianoy Renato Soibelmann,Silveira Rita C Jornal de pediatria OBJECTIVES:To present current evidence on the etiology, risk factors, diagnosis, and management of early and late neonatal sepsis. SOURCE OF DATA:Non-systematic review of the Medline (PubMed), Scopus, Web of Science, Cochrane, and Google Scholar databases regarding the following terms: neonatal sepsis, early neonatal sepsis, late neonatal sepsis, empirical antibiotic therapy, sepsis calculator, vancomycin, newborn, preterm newborn. DATA SYNTHESIS:Neonatal sepsis is a frequent cause of neonatal morbidity and mortality. Its diagnosis is difficult. Continuous observation of the patient is critical to diagnostic suspicion. When neonatal sepsis is suspected, bacteriological tests should be collected. Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis, and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk. CONCLUSIONS:Newborns constitute a group that is more vulnerable to sepsis. Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis. 10.1016/j.jped.2019.10.004
    Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand. Husada Dominicus,Chanthavanich Pornthep,Chotigeat Uraiwan,Sunttarattiwong Piyarat,Sirivichayakul Chukiat,Pengsaa Krisana,Chokejindachai Watcharee,Kaewkungwal Jaranit BMC infectious diseases BACKGROUND:Early diagnosis of neonatal sepsis is essential to prevent severe complications and avoid unnecessary use of antibiotics. The mortality of neonatal sepsis is over 18%in many countries. This study aimed to develop a predictive model for the diagnosis of bacterial late-onset neonatal sepsis. METHODS:A case-control study was conducted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Data were derived from the medical records of 52 sepsis cases and 156 non-sepsis controls. Only proven bacterial neonatal sepsis cases were included in the sepsis group. The non-sepsis group consisted of neonates without any infection. Potential predictors consisted of risk factors, clinical conditions, laboratory data, and treatment modalities. The model was developed based on multiple logistic regression analysis. RESULTS:The incidence of late proven neonatal sepsis was 1.46%. The model had 6 significant variables: poor feeding, abnormal heart rate (outside the range 100-180 x/min), abnormal temperature (outside the range 36-37.9 °C), abnormal oxygen saturation, abnormal leucocytes (according to Manroe's criteria by age), and abnormal pH (outside the range 7.27-7.45). The area below the Receiver Operating Characteristics (ROC) curve was 95.5%. The score had a sensitivity of 88.5% and specificity of 90.4%. CONCLUSION:A predictive model and a scoring system were developed for proven bacterial late-onset neonatal sepsis. This simpler tool is expected to somewhat replace microbiological culture, especially in resource-limited settings. 10.1186/s12879-020-4875-5
    Antimicrobial Sensitivity Pattern in Neonatal Sepsis in Neonatal Intensive Care Unit of Mymensingh Medical College Hospital. Amin S E,Hossain M A,Akhtaruzzaman M,Choudhury M F,Islam N,Hossain C F,Akter F,Eva E N,Nasrin K N,Islam M N Mymensingh medical journal : MMJ This cross-sectional descriptive study was conducted at the neonatal intensive care unit (NICU) in the department of Neonatology, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from July 2017 to December 2017 to determine antimicrobial sensitivity pattern in neonatal sepsis. Ninety four neonates (0-28 days) who were admitted in NICU with suspected sepsis were included in this study by purposive sampling technique. After admission written informed consent from parents or guardians obtained and then septic screening along with blood culture and antimicrobial sensitivity was done. All data were compiled, tabulated and then analyzed by SPSS version 21.0. Among 94 cases, 68(72.3%) were preterm and 26(23.4%) were term. There was male predominance and male female ratio was 1.9:1. Most of the patient admitted within 72 hours of birth. Most (84%) had low birth weight (<2500gm). Pre-mature onset of labour, pre-mature rupture of membrane >18 hours, vaginal route of delivery, instrumental resuscitation, pre-lacteal feeding, bottle feeding were the major perinatal risk factors in this study. Early onset sepsis (76.6%) was most prevalent in this study. Blood culture yielded positive growth in 20(21.3%) cases. Among them, Klebsiella was found in 7(35%). E. coli in 6(30%), Acinetobacter was in 3(15%), Staphylococcus aureus in 2(10%) cases. Pseudomonas and Enterobacter were found in rest 2(10%) of the cases. Gram negative bacteria were found in 18(90%) cases. Klebsiella was sensitive to Imipenem (85.7%), Colistin (85.7%) and Ciprofloxacin (77.5%). Sensitivity of E. coli was Imipenem (100%), Colistin (100%), Amikacin (66.7%), Ciprofloxacin (66.7%), Netilmicin (66.7%) and Gentamicin (50%). Acinatobecter had sensitivity to Netilmicin, Colistin, Imipenem (100%). Staphylococcus was 100% sensitive to Imipenem, Netilmicin and Vancomycin. Pseudomonas was found sensitive to Imipenem (100%), Amikacin (100%), Netilmicin (100%) and Colistin (100%). Enterobacter was found highly sensitive to Ciprofloxacin, Colistin and Imipenem. Almost all organisms were resistant to Ampicillin, Gentamicin, Cefotaxime and Ceftazidime. Based on result it is concluded that Klebsiella pneumoniae and Escherichia coli are the leading cause of neonatal sepsis in this study and most of them resistant to multiple antibiotics. Organisms found more sensitive to Imipenem, Colistin, Ciprofloxacin and Netilmicin.
    Factors associated with culture proven neonatal sepsis in the Ho municipality 2016. Aku Fortress Yayra,Akweongo Patricia,Nyarko Kofi Mensah,Mensah Lord Graceful,Amegan-Aho Kokou,Kumi Lawrence,Afari Edwin Andrew,Ameme Donne Kofi,Kenu Ernest The Pan African medical journal Introduction:Neonatal Sepsis (NNS) is a public health problem which causes death or disability unless appropriate antibiotic treatment is given promptly. Globally, sepsis is an important cause of morbidity and mortality in neonates despite recent progress in health care delivery. We assessed the factors associated with culture proven sepsis among neonates in the Ho Municipality, Ghana. Methods:a cross-sectional study was conducted in two public hospitals in the Ho Municipality between January and May, 2016. All neonates who were clinically suspected with sepsis in the Neonatal Intensive Care Unit (NICU) and their mothers were recruited. A 2ml blood sample was taken aseptically and dispensed into a mixture of thioglycollate and tryptone soy broth in a 1: 10 dilution and microbiological procedures performed. Case notes of both neonates and their mothers were reviewed and interviews conducted to collect both clinical and socio-demographic data. We determined the factors associated with culture proven neonatal sepsis using logistic regression model and statistical significance was determined at 95% confidence intervals. Results:out of 150 neonates, 26 (17%) had laboratory confirmed sepsis. The most common pathogen isolated was Staphylococcus epidermidis 14, (54%). Neonates whose mothers were primigravida (OR=2.74; 95% CI: 1.12-6.68), and those who attended antenatal clinics (ANC) fewer than three schedules (OR=2.90; 95% CI: 1.06-7.96) had higher odds of developing culture proven sepsis. Conclusion:neonates who were the first babies of their mothers were more likely to develop laboratory confirmed sepsis. Also, neonates of mothers who attended ANC less than 3 times were more likely to develop laboratory confirmed sepsis. High index of suspicion is required to diagnose neonatal sepsis among neonates of primigravida mothers and mothers who attend fewer than three ANC schedules. 10.11604/pamj.2020.36.281.20408
    Neonatal sepsis in low-income countries: epidemiology, diagnosis and prevention. Popescu Constantin Radu,Cavanagh Miranda M M,Tembo Bentry,Chiume Msandeni,Lufesi Norman,Goldfarb David M,Kissoon Niranjan,Lavoie Pascal M Expert review of anti-infective therapy : Sepsis accounts for up to one-third of neonatal deaths in the world each year. The World Health Organization acknowledges neonatal sepsis as a major global health concern, and that the highest burden occurs in low- and middle-income countries (LMICs). Despite major research and clinical progress in this area, we still lack accurate diagnostic tools for neonatal sepsis, complicating the management of this condition.: The purpose here is to review the latest data on the incidence, diagnosis, prevention, and management of neonatal sepsis in LMIC. We discuss the limitations of current diagnostic tests - including their lack of availability - and how this may influence global estimates of cases. We review the benefits of antenatal, intrapartum, and post-natal preventive measures. We briefly discuss the management, highlighting the emergence of antimicrobial resistance. Finally, we expose some high priority areas.: Neonatal sepsis is a challenging condition requiring a multifaceted approach to address the major diagnostic issues, but also the underlying socio-economic causes that nourish epidemic cases in LMIC. Focusing on antibiotics as a main pillar of intervention is likely to engender antimicrobial resistance, eventually hindering the appreciable gains LMICs have achieved in neonatal health outcomes. 10.1080/14787210.2020.1732818