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Changes in incidence and etiology of early-onset neonatal infections 1997-2017 - a retrospective cohort study in western Sweden. Johansson Gudjónsdóttir Margrét,Elfvin Anders,Hentz Elisabet,Adlerberth Ingegerd,Tessin Ingemar,Trollfors Birger BMC pediatrics BACKGROUND:The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997-2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975. METHODS:Observational epidemiological, retrospective study on infants 0-6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997-2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975. RESULTS:The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997-2007 to 0.9/1000 LB in 2008-2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997-2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987-1996 to 0.45/1000 live births 1997-2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge. CONCLUSION:There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area. KEY NOTES:This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life. 10.1186/s12887-019-1866-z
Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis. Cortés José S,Losada Paula X,Fernández Laura X,Beltrán Emilce,DeLaura Isabel,Narváez Carlos F,Fonseca-Becerra Carlos Eduardo American journal of perinatology OBJECTIVE:The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia. STUDY DESIGN:A nonmatched case-control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS). RESULTS:Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35-112]) were identified as risk factors for NS. Differences in CRP ( < 0.0001) and IL-6 ( < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 ( < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 ( = 0.0315) and the optimal cutoff was 17.75 pg/mL. CONCLUSION:Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group. KEY POINTS:· NS is a major morbimortality cause worldwide. · CRP and IL-6 levels may be useful NS biomarkers. · No biomarker alone is enough for the diagnosis of NS. 10.1055/s-0040-1710010
Predicting Infection in Very Preterm Infants: A Study Protocol. Nursing research BACKGROUND:Neonatal sepsis causes morbidity and mortality in preterm infants. Clinicians need a predictive tool for the onset of neonatal infection to expedite treatment and prevent morbidity. Abnormal thermal gradients, a central-peripheral temperature difference (CPtd) of >2°C or <0°C, and elevated heart rate characteristic (HRC) scores are associated with infection. OBJECTIVE:This article presents the protocol for the Predictive Analysis Using Temperature and Heart Rate Study. METHODS:This observational trial will enroll 440 very preterm infants to measure abdominal temperature and foot temperature every minute and HRC scores hourly for 28 days to compare infection data. Time with abnormal thermal gradients (Model 1) and elevated HRC scores (Model 2) will be compared to the onset of infections. For data analysis, CPtd (abdominal temperature - foot temperature) will be investigated as two derived variables, high CPtd (number/percentage of minutes with CPtd of >2°C) and low CPtd (number/percentage of minutes with CPtd of <0°C). In the infant-level model, the outcome yi will be an indicator of whether the infant was diagnosed with an infection in the first 28 days of life, and the high CPtd and low CPtd variables will be the average over the entire observation period, logit(yi) = β0 + xiβ1 + ziγ. For the day-level model, the outcome yit will be an indicator of whether the ith infant was diagnosed with an infection on the tth day from t = 4 through t = 28 or the day that infection is diagnosed (25 possible repeated measures), logit(yit) = β0 + xitβ1 + zitγ. It will be determined whether a model with only high CPtd or only low CPtd is superior in predicting infection. Also, the correlation of abnormal HRC scores with high CPtd and low CPtd values will be assessed. DISCUSSION:Study results will inform the design of an interventional study using temperatures and/or heart rate as a predictive tool to alert clinicians of cardiac and autonomic instability present with infection. 10.1097/NNR.0000000000000483
How to assess early-onset neonatal sepsis? Comparison of three detection strategies. Anales de pediatria INTRODUCTION:Early-onset neonatal sepsis (EONS) can cause significant morbidity and mortality, especially if it is not detected early. Given the decrease in its incidence in the past few decades, it is important to find a balance between reducing the use of diagnostic tests and continuing to detect affected patients. We compared 3 detection strategies in patients with risk factors (RFs) for infection: laboratory screening (S1), the Neonatal Sepsis Risk Calculator (S2) and clinical observation (S3). PATIENTS AND METHODS:Retrospective observational study in neonates born at 34 weeks of gestation or later and with RFs or symptoms compatible with EONS. We analysed outcomes in our unit with the use of laboratory screening (S1) and compared them with the other two strategies (S2 and S3) to contemplate whether to modify our protocol. RESULTS:The study included 754 patients, and the most frequent RFs were prolonged rupture of membranes (35.5%) and maternal colonization by Streptococcus agalactiae (38.5%). Strategies S2 and S3 would decrease the performance of laboratory tests (S1, 56.8% of patients; S2, 9.9%; S3, 22.4%; P < 0.01), hospital admissions (S1, 11%; S2, 6.9%; S3, 7.9%; P < 0.01) and the use of antibiotherapy (S1, 8.6%; S2, 6.7%; S3, 6.4%; P < 0.01). Sepsis was diagnosed in 13 patients, and it would have been detected with S2 and S3 except in 1 patient who had asymptomatic bacteriemia by Enterococcus faecalis. No patient with mild and self-limited symptoms in whom antibiotherapy was not started received a diagnosis of sepsis later on. CONCLUSION:Close clinical observation seems to be a safe option and could reduce the use of diagnostic tests, hospital admission and unnecessary antibiotherapy. The watchful waiting approach in patients with mild and self-limiting symptoms in the first hours post birth does not appear to be associated with failure to identify sepsis. 10.1016/j.anpede.2022.10.009
Early-Onset Sepsis Among Very Preterm Infants. Pediatrics OBJECTIVES:To determine the epidemiology and microbiology of early-onset sepsis (EOS) among very preterm infants using a nationally representative cohort from academic and community hospitals to inform empirical antibiotic guidance, highlight risk factors for infection, and aid in prognostication for infected infants. METHODS:Prospective observational study of very preterm infants born weighing 401 to 1500 g or at 22 to 29 weeks' gestational age from January 2018 to December 2019 in 753 Vermont Oxford Network centers. EOS was defined as a culture-confirmed bacterial infection of the blood or cerebrospinal fluid in the 3 days after birth. Demographics, clinical characteristics, and outcomes were compared between infants with and without EOS. RESULTS:Of 84 333 included infants, 1139 had EOS for an incidence rate of 13.5 per 1000 very preterm births (99% confidence interval [CI] 12.5-14.6). (538 of 1158; 46.5%) and group B (218 of 1158; 18.8%) were the most common pathogens. Infected infants had longer lengths of stay (median 92 vs 66 days) and lower rates of survival (67.5% vs 90.4%; adjusted risk ratio 0.82 [95% CI 0.79-0.85]) and of survival without morbidity (26.1% vs 59.4%; adjusted risk ratio 0.66 [95% CI 0.60-0.72]). CONCLUSIONS:In a nationally representative sample of very preterm infants with EOS from 2018 to 2019, approximately one-third of isolates were neither group B nor . Three-quarters of all infected infants either died or survived with a major medical morbidity. The profoundly negative impact of EOS on very preterm infants highlights the need for novel preventive strategies. 10.1542/peds.2021-052456
Antibiotic Use in Term and Near-Term Newborns. Mundal Håkon Stangeland,Rønnestad Arild,Klingenberg Claus,Stensvold Hans Jørgen,Størdal Ketil Pediatrics OBJECTIVES:We aimed to study whether national and local antibiotic stewardship projects have reduced the antibiotic use in newborns and to monitor potential changes in adverse outcomes. METHODS:In a nationwide, population-based study from Norway, we included all hospital live births from 34 weeks' gestation (n = 282 046) during 2015 to 2019. The primary outcome was the proportion of newborns treated with antibiotics from 0 to 28 days after birth. The secondary outcomes were the overall duration of antibiotic treatment and by categories: culture-positive sepsis, clinical sepsis, and no sepsis. RESULTS:A total of 7365 (2.6%) newborns received intravenous antibiotics during the period, with a reduction from 3.1% in 2015 to 2.2% in 2019 (30% decrease; P < .001). Hospitals with antibiotic stewardship projects experienced the largest reduction (48% vs 23%; P < .001). We found a small decrease in the median duration of antibiotic treatment in newborns without sepsis from 2.93 to 2.66 days (P = .011), and geographical variation was reduced during the study period. The overall number of days with antibiotic treatments was reduced by 37% from 2015 to 2019 (119.1 of 1000 vs 75.6 of 1000; P < .001). Sepsis was confirmed by blood culture in 206 newborns (incidence rate: 0.73 cases per 1000 live births). We found no increase in sepsis with treatment onset >72 hours of life, and sepsis-attributable deaths remained at a low level. CONCLUSIONS:During the study period, a substantial decrease in the proportion of newborns treated with antibiotics was observed together with a decline in treatment duration for newborns without culture-positive sepsis. 10.1542/peds.2021-051339
Ten- vs. 14-day antibiotic therapy for culture-positive neonatal sepsis. Journal of tropical pediatrics BACKGROUND:Neonatal sepsis is a major determinant of neonatal mortality. There is a scarcity of evidence-based guidelines for the duration of antibiotics in culture-positive sepsis. OBJECTIVES:The aim of this study was to compare the efficacy of 10- and 14-day antibiotic therapies in the management of culture-positive neonatal sepsis. METHODS:This randomized controlled trial was conducted in the neonatal intensive care unit of a tertiary care center among the neonates suffering from culture-positive sepsis (with signs of clinical remission on day 9 of antibiotic) between January 2023 and May 2023. Newborns with major congenital anomaly, deep-seated infections, multi-organ dysfunction, associated fungal infections/infection by multiple organisms and severe birth asphyxia were excluded. Two hundred and thirty-four newborns were randomized into two groups-study (received 10 days of antibiotics) and control (received 14 days of antibiotics). Treatment failure, hospital stay and adverse effects were compared between the two groups. p < 0.05 was taken as the limit of statistical significance. RESULTS:Median [interquartile range (IQR)] birth weight and gestational age of the study population (53.8% boys) were 2.424 kg (IQR: 2.183-2.695) and 37.3 weeks (IQR: 35.5-38.1), respectively. Acinetobacter was the most commonly isolated species (56, 23.9%). The baseline characteristics of both groups were almost similar. Treatment failure was similar in the study and control groups (3.8% vs. 1.7%, p = 0.40), with a shorter hospital stay [median (IQR): 14 (13-16) vs. 18 (17-19) days, p < 0.001]. CONCLUSION:Ten-day antibiotic therapy was comparable with 14-day antibiotic therapy in efficacy, with a shorter duration of hospital stay and without any significant increase in adverse effects. 10.1093/tropej/fmad036
A randomized clinical trial of antibiotic treatment duration in preterm pre-labor rupture of membranes: 7 days vs until delivery. American journal of obstetrics & gynecology MFM BACKGROUND:Antibiotic treatment in preterm pre-labor rupture of membranes can prolong the interval from membrane rupture to delivery and improve neonatal outcomes. However, the duration of antibiotic treatment for preterm pre-labor rupture of membranes has been rarely compared in prospective studies. OBJECTIVE:This study aimed to investigate the optimal duration of antibiotic treatment for pre-labor rupture of membranes. We performed a randomized controlled trial comparing neonatal morbidity and infantile neurologic outcomes between 2 groups of patients with preterm pre-labor rupture of membranes who received antibiotic treatment for 7 days or until delivery, respectively. STUDY DESIGN:This prospective randomized study included patients who were diagnosed with preterm pre-labor rupture of membranes between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dosage every 12 hours) and oral clarithromycin (500 mg dosage every 12 hours) either for 7 days or until delivery. The study protocol was registered at ClinicalTrials.gov under identifier NCT01503606. The primary outcome was a neonatal composite morbidity, and the secondary outcome was neurologic outcomes at 12 months of corrected age. We enrolled 151 patients and allocated 75 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. RESULTS:After excluding cases lost to follow-up and those with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) patients with preterm pre-labor rupture of membranes and their babies were compared. There was no significant difference in the pregnancy outcomes, including gestational age at delivery and the interval from rupture of membranes to delivery, between the 2 groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rates of respiratory distress syndrome (32.8% vs 50.8%; P=.039) and composite neonatal morbidities (34.4% vs 53.9%; P=.026) were lower in the until-delivery group than in the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, antenatal corticosteroids treatment, gestational age at delivery, interval from rupture of membranes to delivery, and clinical chorioamnionitis. Infantile neurologic outcomes were evaluated in 71.4% of the babies discharged alive and did not differ between the groups. CONCLUSION:Overall, the until-delivery regimen of cefazolin and clarithromycin in preterm pre-labor rupture of membranes led to a lower incidence of composite neonatal morbidity and respiratory distress syndrome than the 7-day regimen, and both regimens otherwise showed similar individual neonatal morbidities and infantile neurologic outcomes. 10.1016/j.ajogmf.2023.100886
Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study. The Lancet. Global health BACKGROUND:Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. METHODS:The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. FINDINGS:Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. INTERPRETATION:Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. FUNDING:Bill & Melinda Gates Foundation. 10.1016/S2214-109X(22)00043-2
Late-Onset Sepsis Among Very Preterm Infants. Pediatrics OBJECTIVES:To determine the epidemiology, microbiology, and associated outcomes of late-onset sepsis among very preterm infants using a large and nationally representative cohort of NICUs across the United States. METHODS:Prospective observational study of very preterm infants born 401 to 1500 g and/or 22 to 29 weeks' gestational age (GA) from January 1, 2018, to December 31, 2020, who survived >3 days in 774 participating Vermont Oxford Network centers. Late-onset sepsis was defined as isolation of a pathogenic bacteria from blood and/or cerebrospinal fluid, or fungi from blood, obtained >3 days after birth. Demographics, clinical characteristics, and outcomes were compared between infants with and without late-onset sepsis. RESULTS:Of 118 650 infants, 10 501 (8.9%) had late-onset sepsis for an incidence rate of 88.5 per 1000 (99% confidence interval [CI] [86.4-90.7]). Incidence was highest for infants born ≤23 weeks GA (322.0 per 1000, 99% CI [306.3-338.1]). The most common pathogens were coagulase negative staphylococci (29.3%) and Staphylococcus aureus (23.0%), but 34 different pathogens were identified. Infected infants had lower survival (adjusted risk ratio [aRR] 0.89, 95% CI [0.87-0.90]) and increased risks of home oxygen (aRR 1.32, 95% CI [1.26-1.38]), tracheostomy (aRR 2.88, 95% CI [2.47-3.37]), and gastrostomy (aRR 2.09, 95% CI [1.93-2.57]) among survivors. CONCLUSIONS:A substantial proportion of very preterm infants continue to suffer late-onset sepsis, particularly those born at the lowest GAs. Infected infants had higher mortality, and survivors had increased risks of technology-dependent chronic morbidities. The persistent burden and diverse microbiology of late-onset sepsis among very preterm infants underscore the need for innovative and potentially organism-specific prevention strategies. 10.1542/peds.2022-058813