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    A Diagnostic Formula for Discrimination of Tuberculous and Bacterial Meningitis Using Clinical and Laboratory Features. Yang Yun,Qu Xin-Hui,Zhang Kun-Nan,Wu Xiao-Mu,Wang Xin-Rong,Wen An,Li Ling-Juan Frontiers in cellular and infection microbiology The discrimination of tuberculous meningitis and bacterial meningitis remains difficult at present, even with the introduction of advanced diagnostic tools. This study aims to differentiate these two kinds of meningitis by using the rule of clinical and laboratory features. A prospective observational study was conducted to collect the clinical and laboratory parameters of patients with tuberculous meningitis or bacterial meningitis. Logistic regression was used to define the diagnostic formula for the discrimination of tuberculous meningitis and bacterial meningitis. A receiver operator characteristic curve was established to determine the best cutoff point for the diagnostic formula. Five parameters (duration of illness, coughing for two or more weeks, meningeal signs, blood sodium, and percentage of neutrophils in cerebrospinal fluid) were predictive of tuberculous meningitis. The diagnostic formula developed from these parameters was 98% sensitive and 82% specific, while these were 95% sensitive and 91% specific when prospectively applied to another 70 patients. The diagnostic formula developed in the present study can help physicians to differentiate tuberculous meningitis from bacterial meningitis in high-tuberculosis-incidence-areas, particularly in settings with limited microbiological and radiological resources. 10.3389/fcimb.2019.00448
    Psychiatric Disabilities and Other Long-term Consequences of Childhood Bacterial Meningitis. Johansson Kostenniemi Urban,Bazan Aleksander,Karlsson Linda,Silfverdal Sven-Arne The Pediatric infectious disease journal BACKGROUND:Bacterial meningitis is known to cause hearing impairments and neurologic deficits; however, less is known regarding psychiatric disabilities. In this study, we assessed psychiatric disabilities and other long-term consequences of childhood bacterial meningitis. METHODS:From a previously validated dataset, we selected children having had bacterial meningitis. We then reviewed medical records and child health records from discharge onwards to identify disabilities. We calculated the occurrence of disabilities with a 95% confidence interval (CI), and we used a χ test to assess possible individual risk factors associated with occurrence of disabilities. RESULTS:Of the 80 children included in this study, permanent disabilities not attributed to preexisting diseases were noted in 56% (CI: 45-67) during the mean observation period of 19 years and 2 months. Psychiatric disease was diagnosed in 30% (CI: 21-41), and another 5% (CI: 2-13) were under ongoing investigations for symptoms of psychiatric disease. Hearing impairments affected at least 30% (CI: 20-40), and neurologic deficits affected at least 23% (CI: 15-34). While other disabilities were often detected within the first year, psychiatric disabilities were detected after a mean time period of 14 years (CI: 11:1-16:11). Although some associations were noted, no individual risk factor was able to predict the occurrence of disabilities. CONCLUSIONS:Psychiatric disabilities affect more than one-third of survivors and are among the most common long-term consequence of childhood bacterial meningitis. Late discovery and predictive difficulties call for a revision of current guidelines to include a specific long-term strategy for detecting psychiatric disabilities. 10.1097/INF.0000000000002908
    Extended Continuous β-Lactam Infusion With Oral Acetaminophen in Childhood Bacterial Meningitis: A Randomized, Double-blind Clinical Trial. Savonius Okko,Rugemalira Emilie,Roine Irmeli,Cruzeiro Manuel Leite,Peltola Heikki,Pelkonen Tuula Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:In our previous study in Luanda, Angola, initial continuous β-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further. METHODS:We conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250 mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/kg, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7. RESULTS:In all, 375 patients were included in the study between 22 January 2012 and 21 January 2017. As 2 children succumbed before treatment initiation, 187 vs 186 participants remained in the intervention and control groups, respectively. On day 7, 61 of 187 (32.6%) children in the intervention group vs 64 of 186 (34.4%) in the control group had died (risk ratio, 0.95 [95% confidence interval {CI}, .71-1.26]; absolute risk difference, 1.8% [95% CI, -7.8 to 11.4]). At discharge from hospital, the corresponding numbers were 71 of 187 (38.0%) and 75 of 186 (40.3%), respectively. CONCLUSIONS:Prolonged continuous β-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola. CLINICAL TRIALS REGISTRATION:NCT01540838. 10.1093/cid/ciaa341
    Treatment Outcomes and Associated Factors among Children Hospitalized with Acute Bacterial Meningitis in Eastern Ethiopia: A Cross-Sectional Study. Adem Fuad,Tasew Amanuel,Siraj Ammas,Mohammed Mesud Patient related outcome measures Background:Bacterial meningitis is a common central nervous system infection that is associated with high morbidity and mortality in pediatrics. In Ethiopia, little is known about treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children. Objective:To assess treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children with acute bacterial meningitis in the Hiwot Fana Specialized University Hospital pediatric ward. Methods:A retrospective cross-sectional study was conducted at the pediatric ward of Hiwot Fana Specialized University Hospital, eastern Ethiopia. Relevant data were collected using a structured data-collection tool from patients' medical charts. Bivariate and multivariate logistic regression analyses were done to identify predictors of treatment outcomes. OR with 95% CI and ≤0.05 was used for statistical significance. Results:A total of 200 children with acute bacterial meningitis were included in the study, of which 92% were aged ≥2 months and the majority (128, 64%) had delayed (≥72 hours) presentation to the hospital. At admission, 181 (90.5%) were febrile, 92 (46%) had depressed level of consciousness, and 40 (20%) had had seizures. Most (126, 63%) had documented medical comorbidities. The antibiotic combination of ampicillin and gentamycin had been frequently administered in children aged <2 months while ceftriaxone was commonly prescribed for those aged >2 months. Of the total study participants, 154 (77%) showed successful treatment outcomes, while 46 (23%) experienced poor treatment outcomes (died or "self"-discharged). Level of consciousness (AOR 3.25, 95% CI 1.21-8.75), duration of illness before admission (AOR 3.74, 95% CI 1.76-7.98), and antibiotic-regimen change (AOR 4.7, 95% CI 2.4-10) were predictors of treatment outcomes. Conclusion:The majority of study participants experienced good treatment outcomes. Unconsciousness, antibiotic-regimen change, and duration of illness before hospitalization were significantly associated with treatment outcomes. Early treatment, linkage of primary-health facilities to tertiary health-care centers, and availability of diagnostics should be promoted to improve patient outcomes. 10.2147/PROM.S277586
    Clinical features of bacterial meningitis among hospitalised children in Kenya. Obiero Christina W,Mturi Neema,Mwarumba Salim,Ngari Moses,Newton Charles R,van Hensbroek Michaël Boele,Berkley James A BMC medicine BACKGROUND:Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days. METHODS:We conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/μL, or CSF to blood glucose ratio <0.1. RESULTS:Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77-92) and specificity of 38% (95% CI 37-38). Exclusion of 'fever without malaria parasitaemia' reduced sensitivity to 58% (95% CI 48-68) and increased specificity to 80% (95% CI 79-80). IMCI signs had a sensitivity of 80% (95% CI 70-87) and specificity of 62% (95% CI 61-63). CONCLUSIONS:A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs. 10.1186/s12916-021-01998-3
    Bulging fontanelle in febrile infants as a predictor of bacterial meningitis. Takagi Dania,Oren-Ziv Amit,Shles Ayelet,Schujovitzky Dana,Yechiam Hadas,Rosenbloom Ehud European journal of pediatrics It is common practice to perform a lumbar puncture in infants presenting with fever and a bulging fontanelle in order to rule out bacterial meningitis. However, most of these infants have benign, self-limiting diseases. The objective was to determine whether there is an association between bulging fontanelle and bacterial meningitis in febrile infants. This retrospective cohort study included febrile children with a bulging fontanelle who underwent lumbar puncture at Meir Medical Center from 2005 through 2015. A total of 764 children ages 2-18 months underwent lumbar puncture during the study period. Among them, 304 had a bulging fontanelle and fever on evaluation and cerebrospinal fluid pleocytosis was found in 115 (37.8%), including 1 case of bacterial meningitis (0.3%). None of the infants described on admission as appearing well on presentation was found to have bacterial meningitis. Of the 764 children who underwent lumbar puncture, 10 infants were diagnosed with bacterial meningitis, and only one (10%) presented with a bulging fontanelle.Conclusion: The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis. Most causes of a bulging fontanelle in febrile infants are self-limiting diseases. The routine approach of performing a lumbar puncture in febrile infants with a bulging fontanelle should be reconsidered. What is Known: • It is common to perform a lumbar puncture in febrile infants with a bulging fontanelle, to rule out bacterial meningitis. • However, there are only few researches regarding the relationship between bulging fontanelle and bacterial meningitis. What is New: • The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis • The need for routine lumbar puncture in these cases should be reconsidered. 10.1007/s00431-020-03865-4
    MeningiSSS: A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis. Johansson Kostenniemi Urban,Karlsson Linda,Silfverdal Sven-Arne,Mehle Christer Neurocritical care BACKGROUND:Knowing the individual child's risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors. METHODS:We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure. RESULTS:For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores' results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson-Todd Scale (AUC = 0.79) was all associated with death. CONCLUSIONS:The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management. 10.1007/s12028-019-00792-7
    Changing Epidemiology of Bacterial Meningitis Since Introduction of Conjugate Vaccines: 3 Decades of National Meningitis Surveillance in The Netherlands. Koelman Diederik L H,van Kassel Merel N,Bijlsma Merijn W,Brouwer Matthijs C,van de Beek Diederik,van der Ende Arie Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:The epidemiology of acute bacterial meningitis has changed substantially since the introduction of conjugate vaccines. METHODS:We analyzed nationwide surveillance data of all cerebrospinal fluid isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis in the Netherlands. We assessed the impact of conjugate vaccines on incidence (defined as episodes per 100 000 population per year) and for different age groups using incidence rate ratios (IRRs), comparing incidence before and after conjugate vaccine introduction. RESULTS:We analyzed 17 393 episodes, of which 5960 episodes (34%) occurred in preschool children (aged 3 months to 4 years). Overall, bacterial meningitis incidence decreased from 6.37 to 1.58 between 1989-1993 and 2014-2019 (IRR, 0.25 [95% confidence interval {CI}, .23-.26]; P < .001). This decrease was most pronounced in preschool and school-aged children (5-15 years); IRR, 0.10 [95% CI, .09-.12] and 0.08 [95% CI, .06-.10]; both P < .001. The incidence was highest in young infants (<90 days) due to a high incidence of group B Streptococcus and Escherichia coli meningitis (42.48 and 19.49, respectively). Conjugate vaccines effectively reduced the incidence of Haemophilus influenzae type b, Neisseria meningitidis serogroup C, and 10 pneumococcal serotypes (IRRs, .02-.04; P < .001). At the end of the observed period, Streptococcus pneumoniae caused the majority of meningitis cases (829/1616 [51%]), mostly in older adults (aged 45-64 years) and elderly adults (aged ≥65 years; incidence of 1.06 and 1.54, respectively). CONCLUSIONS:Conjugate vaccines reduced the burden of bacterial meningitis, especially in children. The efforts for new measures to prevent bacterial meningitis should be focused on neonates and elderly, as the residual rate of disease is still high in these age groups. 10.1093/cid/ciaa1774
    Hospital-based sentinel surveillance for bacterial meningitis in under-five children prior to the introduction of the PCV13 in India. Jayaraman Yuvaraj,Veeraraghavan Balaji,Girish Kumar C P,Sukumar Bharathy,Rajkumar Prabu,Kangusamy Boopathi,Verghese Valsan Philip,Varghese Rosemol,Jayaraman Ranjith,Kapoor Ambujam Nair,Gupta Nivedita,Kanagasabai K,David Joseph K,Rajaraman Jayasri,Sockalingam Gowtham,Khera Ajay,Haldar Pradeep,Aggarwal M K,Pillai Rajamohanan K,Manchanda Vikas,Theodore Ramani Bai Joseph,Rajahamsan Jyothi,Mohan Girija,Jayalekshmi V,Nedunchelian Krishnamoorthy,Devasena N,Sridharan Sujatha,Selvi R,Ravinder T,Narayana Babu R,Mathevan G,Sugumari C,Sugandhi Rao P,Kini Pushpa G,Dwibedi Bhagirathi,Kanga Anil,Grover Neelam,Narayanan Harish,Mehendale Sanjay M Vaccine INTRODUCTION:A hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals. METHODS:We enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS:Among 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates. CONCLUSIONS:The results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India. 10.1016/j.vaccine.2021.05.041
    Blood Procalcitonin Level as a Diagnostic Marker of Pediatric Bacterial Meningitis: A Systematic Review and Meta-Analysis. Kim Heeyeon,Roh Yun-Ho,Yoon Seo-Hee Diagnostics (Basel, Switzerland) Early diagnosis and treatment of bacterial meningitis in children are essential, due to the high mortality and morbidity rates. However, lumbar puncture is often difficult, and cerebrospinal fluid (CSF) culture takes time. This meta-analysis aims to determine the diagnostic accuracy of blood procalcitonin for detecting bacterial meningitis in children. We conducted a systematic search on electronic databases to identify relevant studies. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated, and a hierarchical summary receiver operating characteristic curve and area under the curve (AUC) were determined. Eighteen studies with 1462 children were included in the analysis. The pooled sensitivity, specificity, and the DOR of blood procalcitonin for detecting bacterial meningitis were 0.87 (95% confidence interval (CI): 0.78-0.93); 0.85 (95% CI: 0.75-0.91), and 35.85 (95% CI: 10.68-120.28), respectively. The AUC for blood procalcitonin was 0.921. Blood procalcitonin also showed higher diagnostic accuracy for detecting bacterial meningitis than other conventional biomarkers, including serum C-reactive protein and leukocyte count, CSF leukocyte and neutrophil count, and CSF protein and glucose levels. Blood procalcitonin can be a good supplemental biomarker with high diagnostic accuracy in detecting bacterial meningitis in children. 10.3390/diagnostics11050846
    Characterization of the Blood and Cerebrospinal Fluid Microbiome in Children with Bacterial Meningitis and Its Potential Correlation with Inflammation. Liao Huiping,Zhang Yuchao,Guo Wei,Wang Xi,Wang Hailong,Ye Haocheng,Wu Kai,Zhang Yu-Hang,Guo Lingyun,Zhu Yufei,Guo Yongli,Hu Landian,Liu Gang,Kong Xiangyin mSystems Bacterial meningitis shows a higher incidence in children than adults, but signs may be scarce. Although some pathogenic microorganisms of meningitis from cerebrospinal fluid (CSF) have been reported, the signature of the representative microbiota in CSF and blood samples from patients remains incompletely revealed. To extend the understanding of the microbiome in patients, we recruited 32 children with bacterial meningitis, 30 undiagnosed infectious children, and 10 matched healthy individuals, which was followed by untargeted metagenomic next-generation sequencing (mNGS) and bioinformatic analysis. Our results showed that children with bacterial meningitis exhibited different microbiome signatures in their CSF and blood compared with undiagnosed and healthy children, and patients could be divided into varied subsets according to these signatures, including Escherichia coli, Klebsiella pneumoniae, Thermothelomyces thermophila, Lactobacillus acidophilus, and Staphylococcus haemolyticus. To further explore their potential role in patients' conditions, we examined their correlation with clinical parameters. Importantly, microbiome signatures with compositional changes were correlated with the C-reactive protein (CRP) level in blood and granulocyte percentage in CSF. Moreover, the blood in subsets of patients with a predominance of Klebsiella pneumoniae could replace CSF as the main specimen for clinical monitoring. This study revealed the microbial compositions in children with bacterial meningitis who were treated with antibiotics and made a comprehensive comparison between blood and CSF specimens for the risk and prognosis assessment. We found that microbiome signatures could distinguish patient subsets in the children and were correlated with the CRP level in blood and granulocyte percentage in CSF. The compositional changes in representative microbiota constituents could provide guidance for clinical monitoring and antibiotic intervention. 10.1128/mSystems.00049-21
    Nationwide Population-Based Epidemiological Study for Outcomes of Adjunctive Steroid Therapy in Pediatric Patients with Bacterial Meningitis in Taiwan. Hsieh Dong-Yi,Lai Yun-Ru,Lien Chia-Yi,Chang Wen-Neng,Huang Chih-Cheng,Cheng Ben-Chung,Kung Chia-Te,Lu Cheng-Hsien International journal of environmental research and public health Although corticosteroids can serve as an effective anti-inflammatory adjuvant therapy, the role of adjunctive steroid therapy in pediatric bacterial meningitis in Taiwan remains under-investigated. Cases of acute bacterial meningitis, aged between 1 month and 20 years, were divided into a steroid group (empirical antibiotics with adjunctive steroid therapy) and a non-steroid group (empirical antibiotics only). Data were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database using the International Classification of Diseases, Ninth Revision codes. Of the 8083 episodes enrolled in this study, 26% (2122/8083) and 74% (5961/8083) were divided into the steroid and non-steroid groups, respectively. The fatality rates were 7.9% in the steroid group and 1.7% in the non-steroid group during hospitalization ( < 0.0001). In the steroid and non-steroid groups, the median length of hospital stay was 13 and 6 days, respectively ( < 0.0001). Medical costs (median (interquartile range)) of hospitalization were 77,941 (26,647-237,540) and 26,653 (14,287-53,421) New Taiwan dollars in the steroid and non-steroid groups, respectively ( < 0.0001). The steroid group had a more fulminant course at baseline, a higher fatality rate, length of hospital stay, and medical cost of hospitalization. Therefore, the beneficial effects of the adjunctive use of corticosteroids in pediatric bacterial meningitis are inconclusive, and additional prospective multicenter investigations are required to clarify this issue. 10.3390/ijerph18126386
    Genetic variations of toll-like receptors: Impact on susceptibility, severity and prognosis of bacterial meningitis. Zheng Kai,He Felix B,Liu Hongshan,He Qiushui Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases Bacterial meningitis (BM) is a serious infectious disease of the central nervous system,which is mainly caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Group B Streptococcus and Listeria monocytogenes. Throughout the world, BM has become one of the most lethal diseases that commonly occurs in children. Toll like receptors (TLRs) are one of the most important immune defense lines in infectious diseases, and play an essential role in host defense. Accumulating evidence shows that genetic variations in TLRs are associated with host responses in BM. This review aims to summarize the role of different TLRs and their genetic variations in the susceptibility, severity and prognosis of BM and discuss the identified risk factors for better treatment and improvement of the course and outcome of BM. 10.1016/j.meegid.2021.104984
    Predictors of Neurodevelopmental Impairment After Neonatal Bacterial Meningitis. Haffner Darrah N,Machie Michelle,Hone Emily,Said Rana R,Maitre Nathalie L Journal of child neurology BACKGROUND:Neonatal bacterial meningitis has high rates of morbidity and mortality. Early clinical signs and neuroimaging suggest adverse outcomes, but little is known about their combined predictive properties. We evaluated the combination of findings most associated with death and neurodevelopmental impairment. METHODS:Single-center retrospective cohort study of term and late preterm neonates with bacterial meningitis. Predictors of death and neurodevelopmental impairment were identified on univariate analysis and incorporated into Lasso models to identify variables best predicting adverse outcomes. RESULTS:Of 103 neonates, 6 died acutely; 30% of survivors had neurodevelopmental impairment. Clinical variables (seizures, pressor support) predicted death and neurodevelopmental impairment better than the neuroimaging or combined findings (area under the curve 0.88 vs 0.79 and 0.83, respectively). Among survivors, neuroimaging findings (cerebrovascular lesions, ventriculomegaly) predicted neurodevelopmental impairment better than clinical or combined findings (area under the curve 0.82 vs 0.80 and 0.77, respectively). CONCLUSIONS:Seizures are important predictors of adverse outcomes in neonatal bacterial meningitis. Among survivors, neuroimaging findings help predict neurodevelopmental impairment. 10.1177/08830738211026053
    Eliminating Lumbar Puncture for Low-Risk Febrile Infants: A Quality Improvement Initiative. Gala Payal K,Scarfone Richard J,Murray Ashlee,Balamuth Fran Pediatric emergency care BACKGROUND:Bacterial meningitis in low-risk febrile young infants (FYIs) aged >28 days has become increasingly rare. Routine performance of lumbar puncture (LP) in these infants is associated with adverse consequences and may be unnecessary. We modified our clinical practice guideline (CPG) to reduce the number of FYIs 29 to 56 days old who receive LP. METHODS:This quality improvement project sought to modify a preexisting CPG to diagnose and manage FYIs 0 to 56 days old that eliminated routine performance of LP in children 29 to 56 days old who were considered low-risk for serious bacterial infection. The change was implemented by making adjustments to the online CPG. A statistical process control chart was used to assess the affect of the initiative on our primary outcome of LP rate in this population of FYIs. RESULTS:Postimplementation of the CPG initiative, 71% of FYIs 29 to 56 days old did not receive LP, compared with 42% preimplementation. This practice change was also associated with fewer hospitalizations, lower median emergency department (ED) length of stay, and fewer 72-hour ED revisits. Over 3 years of sustained practice, 1/713 (0.1%; 95% confidence interval, 0%-0.8%) low-risk FYI returned within 72 hours and was subsequently treated for probable bacterial meningitis, although cerebrospinal fluid culture was negative for bacterial growth. CONCLUSIONS:A change in CPG reduced the number of LPs performed in febrile infants 29 to 56 days old. This change resulted in fewer LPs, hospitalizations, ED revisits, and a lower ED length of stay for FYIs 29 to 56 days old. 10.1097/PEC.0000000000002494
    Prevalence and risk factors of seizure in children with acute bacterial meningitis: updating previous evidence using an epidemiological design. Ataei Nakhaei Alireza,Bakhtiari Elham,Ghahremani Sara,Akhondian Javad,Sasan Mohammad Saeed,Movahed Malihe,Aelami Mohammad Hassan Iranian journal of child neurology Objective:The current study aimed to investigate the prevalence and risk factors of seizure in acute bacterial meningitis. Materials & Methods:In the present study, a total of 180 children (age range, 2 months to 14 years) with acute bacterial meningitis, were separated into two groups based on the diagnosis of seizure. The study was conducted in Mashhad (Iran) from 2002 to 2016. Results:Seizure occurred in 37.4% of children with bacterial meningitis. () was the most common organism. Most of the children with seizures (53.7%) had more than one episode. Also, 35% of patients had neurologic complications. Complications were more related to the seizure occurrence, the number of episodes, prolonged seizure, and being younger than 12 months. Age categories of less than 1 year and 1-5 year were associated with increased risk of seizure (odds ratio: 4.33 and 6.54, respectively). The more episode of seizure was associated with more complications (odds ratio: 6.33). Conclusion:The prevalence of seizures in acute bacterial meningitis was 37.4%. Besides, the seizure was associated with more complications. Hence, timely diagnosis and treatment of bacterial meningitis are necessary for preventing future consequences. 10.22037/ijcn.v15i2.22250
    Health-related Quality of Life After Childhood Bacterial Meningitis. Rugemalira Emilie,Karppinen Mariia,Savonius Okko,Cruzeiro Manuel Leite,Peltola Heikki,Roine Irmeli,Pelkonen Tuula The Pediatric infectious disease journal BACKGROUND:Survivors of bacterial meningitis (BM) often suffer from impaired quality of life that stems from disabling sequelae. The authors aimed to estimate health-related quality of life (HRQOL) and the influence of neurologic and audiologic sequelae among pediatric BM survivors. METHODS:Survivors of 2 BM treatment trials at Luanda Children's Hospital, Angola were evaluated for severity of disability via the modified Glasgow Outcome Scale, which considers neurologic and audiologic sequelae. Children who received vaccinations at the hospital during the time of the study (1-2, 2017) and survivors' siblings served as controls. The Pediatric Quality of Life Inventory tool (PedsQL) enabled identifying HRQOL disparities between the cases and controls. RESULTS:In all, 68 BM survivors (median time since BM: 28 months) and 35 controls participated. Survivors scored significantly lower than controls per PedsQL parent-proxy reports, indicating lower HRQOL (physical health: 82.5 vs. 100, P = 0.001; psychosocial health: 80 vs. 90, P = 0.005; and total score: 82.61 vs. 93, P = 0.004), while no difference prevailed between cases and controls in PedsQL child self-reporting. In all Glasgow Outcome Scale classes, cases differed significantly from controls in PedsQL parent-proxy reporting terms, with total scores of 84.21 (mild/no disability), 43.54 (moderate disability) and 55.56 (severe disability), while the controls scored 91.3 (P = 0.04, P = 0.02 and P < 0.001, respectively). CONCLUSIONS:Irrespective of possible disability, BM survivors' HRQOL is impaired, according to parents' perceptions. There is a need to facilitate follow-ups for all BM survivors, to enable timely rehabilitation when needed. 10.1097/INF.0000000000003243
    [Characteristics and recovery of hearing loss in 573 patients with bacterial meningitis]. Shi J F,Liu H H,Dou Z Z,Guo L Y,Feng W Y,Zhou Y,Li Y,Jin X,Hu H L,Zheng Z P,Liu B,Hu B,Chen T M,Guo X,Chen H Y,Liu G Zhonghua er ke za zhi = Chinese journal of pediatrics To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis. This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children's Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study (=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents' evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss (=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss. 10.3760/cma.j.cn112140-20210511-00409
    Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree. Babenko Dmitriy,Seidullayeva Aliya,Bayesheva Dinagul,Turdalina Bayan,Omarkulov Baurzhan,Almabayeva Aigul,Zhanaliyeva Marina,Kushugulova Almagul,Kozhakhmetov Samat BioMed research international Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis. 10.1155/2021/5519436
    Update and advances in community acquired bacterial meningitis. Hasbun Rodrigo Current opinion in infectious diseases PURPOSE OF REVIEW:Community-acquired bacterial meningitis continues to occur and be associated with significant morbidity and mortality despite the availability of effective conjugate vaccines for the three most important meningeal pathogens. RECENT FINDINGS:Indications for cranial imaging in suspected bacterial meningitis varies significantly between guidelines. Cranial imaging is of no clinical utility in those patients without indications and fosters delays in performing a lumbar puncture. Delaying lumbar puncture is associated with increased costs in both adults and children with meningitis and previous antibiotic therapy impacts the yield of microbiological results. Delaying antibiotic therapy is associated with worse clinical outcomes. Adjunctive steroids have reduced the mortality of adults with pneumococcal meningitis but have been associated with increased adverse outcomes in Listeria monocytogenes and Cryptococcus neoformans. SUMMARY:Community-acquired bacterial meningitis remains a global health concern with high morbidity and mortality especially in low-income countries. Cranial imaging should be done only in patients with an indication with an attempt to do a prompt lumbar puncture and to initiate antibiotic therapy and adjunctive steroids as soon as possible to improve clinical outcomes. 10.1097/QCO.0000000000000543
    Predictive value of repeated cerebrospinal fluid parameters in the outcomes of bacterial meningitis in infants <90 days of age. Ting Joseph Y,Roberts Ashley,Khan Sarah,Bitnun Ari,Hawkes Michael,Barton Michelle,Bowes Jennifer,Brophy Jason,Ouchenir Lynda,Renaud Christian,Boisvert Andrée-Anne,McDonald Jane,Robinson Joan L PloS one BACKGROUND:There are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis. OBJECTIVE:To evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort. METHODS:This cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians. RESULTS:Forty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%. CONCLUSION:In this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital. 10.1371/journal.pone.0238056
    Epidemiology, clinical profile and role of rapid tests in the diagnosis of acute bacterial meningitis in children (aged 1-59 months). Chauhan Divya,Mokta Kiran,Kanga Anil,Grover Neelam Neurology India Objectives:To study the epidemiology, clinical profile, and the role of rapid tests in the diagnosis of acute bacterial meningitis (ABM) in children (1-59 months). Materials and Methods:A total of 250 cerebrospinal fluid (CSF) and 187 blood samples received from clinically suspected cases of ABM were processed based on standard microbiological protocols. CSF samples were also subjected to antigen and nucleic acid detection. Antibiotic susceptibility testing was done according to the Clinical Laboratory Standards Institute guidelines. Children were also evaluated for outcomes and were followed up until 6 months after discharge. Results:Eighty one cases were reported to be having clinically confirmed ABM, out of which group B Streptococcus was the most common pathogen detected in 49.3% (40) patients followed by Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae type b, Escherichia coli, Klebsiella pneumoniae, and Neisseria meningitidis ACYW135 in 23.4% (19), 7.4% (6), 6.1% (5), 6.1% (5), 6.1% (5), and in 1.2% (1) patients, respectively. Complications were observed in 54.3% of the children. A follow-up of 6 months after discharge was possible in 39.5% (32) patients among whom sequelae were recorded in 93.7% (30) patients. Conclusion:ABM remains a major cause of neurological sequelae worldwide. Although culture is the gold standard test for its detection, the investigation takes a longer time and the results are influenced by prior antimicrobial therapy. In such cases, rapid tests aid in the early diagnosis of ABM for instituting appropriate management. 10.4103/0028-3886.236972
    [Analysis of current epidemiological and clinical characteristics for laboratory confirmed epidemic cerebrospinal meningitis cases in Shandong Province, 2007-2016]. Zhang Y,Song L Z,Liu G F,Li M S,Lin X J,Xu A Q Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] To analyze epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases. Epidemiological and clinical informations and cerebrospinal fluid (CSF) and blood specimens of AMES (acute meningitis/encephalitis syndrome) cases were collected in the six sentinel hospitals from 2007 to 2016. () species and serogroup identification were detected by the methods of real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and bacterial culture, and epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases were analyzed. 6 809 AMES cases were reported from 2007 to 2016. Total 4 422 cases were detected, and 90 cases were positive. Through the methods of Real-time PCR, bacterial blood culture and CSF culture, the numbers of positive cases were 90, 2 and 1 respectively. Twenty-two cases were identified from 2007 to 2011 (4 cases were ungrouped), which with the highest incidence in serogroup C cases (17/18), and one cases was ungroupable . laboratory confirmed cases (68 cases) were increased dramatically and mainly occurred in serogroup B cases (43/67, 64.2%) from 2012 to 2016, with serogroup C cases highly decreased (5/67, 7.5%) and ungroupable cases increased (13/67, 19.4%) meanwhile. Serogroup W135 and X cases were first detected at 2012 and 2014, and serogroup A remaining a low level which only detected one case at 2013. The morbidity of epidemic cerebrospinal meningitis was occured in the whole year, and mainly in winter and spring. The ratio of laboratory confirmed cases to AMES cases during November to May (3.5%, 67/1 920) was higher than that during June to October (0.9%, 23/2 502) (χ(2)=34.45, 0.001). Most cases were children, students and farmers, and account for 30.0% (27/90), 31.1% (28/90), 18.9% (17/90), respectively. The majority of cases were under 20 years old (60/90, 66.67%), and serogroup C cases (17/22, 77.3%) mainly occurred in over 12 years old population, while serogroup B (24/43, 55.8%) and ungroupable (6/14) cases mainly occurred in under 12 years old population. The main clinical symptoms of epidemic cerebrospinal meningitis cases were fever (78/90, 86.7%), headache (59/90, 65.6%) and vomiting (51/90, 56.7%). Misdiagnosis rate of admitting diagnosis was up to 87.8% (79/90) for the reason of atypical features in specific symptoms and blood or CSF positive index. The well-healed ratio in correct diagnosed group (7/11) was higher than that in misdiagnosed group (2.5%, 2/79) (χ(2)=40.61, 0.001). The clinical symptoms of epidemic cerebrospinal meningitis cases were atypical, and the diagnosed sensitivity and accuracy would be improved by enhanced molecular biology detection. The predominant epidemic serogroup of switched from serogroup C to B, and the key work was surveaylance of serogroup transition. 10.3760/cma.j.issn.0253-9624.2019.02.009
    A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital. Boudet Agathe,Pantel Alix,Carles Marie-Josée,Boclé Hélène,Charachon Sylvie,Enault Cécilia,Stéphan Robin,Cadot Lucile,Lavigne Jean-Philippe,Marchandin Hélène PloS one Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required. 10.1371/journal.pone.0223887
    [Therapeutic monitoring of cerebrospinal fluid vancomycin concentrations and analysis of their influencing factors in neurosurgical intensive care unit patients]. Yao Mingli,Li Jingchao,Shi Lei,Li Yan,Wang Lingyan,Guan Xiangdong,Ouyang Bin Zhonghua wei zhong bing ji jiu yi xue OBJECTIVE:To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS:A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS:A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS:It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration. 10.3760/cma.j.issn.2095-4352.2019.10.014
    Factors associated with early complications in inpatients who were treated in our clinic between 1992 and 2011 with a diagnosis of acute bacterial meningitis. Bor Meltem,Çokuğraş Haluk Turk pediatri arsivi Aim:To evaluate factors associated with the development of early complications in acute bacterial meningitis. Material and Methods:In our study, 389 patients diagnosed with acute bacterial meningitis between January 1992 and January 2011 at Cerrahpaşa Medical Faculty were retrospectively analyzed to determine the risk factors for the development of early complications. Results:The causative agent was in 17% of cases, S. pneumoniae in 13.6%, and in 6.4%. In 55.5% of cases, the causative agent could not be identified. The mortality rate was found as 1% and the early complication rate was 27.8%. The complications observed included septic shock and disseminated intravascular coagulation (33.3%), hydrocephalus (23.1%), subdural effusion (19.4%), and epilepsy (12%). Risk factors for early complications included being aged below two years (p<0.010), restlessness (p<0.010), rash (p<0.010), leukocytosis in complete blood count (p<0.010), and a cerebrospinal fluid glucose level of <45 mg/dL (p<0.010). Three of the four patients who died were male. The incidence of hydrocephalus was higher in patients who used ampicillin-cefotaxime and who did not receive steroid therapy before treatment (p<0.050). Conclusion:When acute bacterial meningitis is treated properly and adequately, recovery without sequela is possible. Knowing the risk factors for early complications will guide in the monitoring of patients and decrease morbidity and mortality rates. 10.14744/TurkPediatriArs.2019.34445
    Pathogen Analysis of Central Nervous System Infections in a Chinese Teaching Hospital from 2012-2018: A Laboratory-based Retrospective Study. Tian Lei,Zhang Zhen,Sun Zi-Yong Current medical science Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3% (677/785), 9.4% (74/785) and 4.3% (34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1% (15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7% (39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5% (98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8% (93/785) and 7.6% (60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics. 10.1007/s11596-019-2058-7
    [Analysis of pathogenic bacteria and drug resistance in neonatal purulent meningitis]. Zhu Minli,Hu Qianhong,Mai Jingyun,Lin Zhenlang Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To study the clinical characteristics, pathogenic bacteria, and antibiotics resistance of neonatal purulent meningitis in order to provide the guide for early diagnosis and appropriate treatment. METHOD:A retrospective review was performed and a total of 112 cases of neonatal purulent meningitis (male 64, female 58) were identified in the neonatal intensive care unit of Yuying Children's Hospital of Wenzhou Medical University seen from January 1, 2004 to December 31, 2013. The clinical information including pathogenic bacterial distribution, drug sensitivity, head imageology and therapeutic outcome were analyzed. Numeration data were shown in ratio and chi square test was applied for group comparison. RESULT:Among 112 cases, 46 were admitted from 2004 to 2008 and 66 from 2009 to 2013, 23 patients were preterm and 89 were term, 20 were early onset (occurring within 3 days of life) and 92 were late onset meningitis (occurring after 3 days of life). In 62 (55.4%) cases the pathogens were Gram-positive bacteria and in 50 (44.6%) were Gram-negative bacteria. The five most frequently isolated pathogens were Escherichia coli (32 cases, 28.6%), coagulase-negative staphylococcus (CNS, 20 cases, 17.9%), Streptococcus (18 cases, 16.1%, Streptococcus agalactiae 15 cases), Enterococci (13 cases, 11.6%), Staphylococcus aureus (9 cases, 8.0%). Comparison of pathogenic bacterial distribution between 2004-2008 and 2009-2013 showed that Gram-positive bacteria accounted for more than 50% in both period. Escherichia coli was the most common bacterium, followed by Streptococcus in last five years which was higher than the first five years (22.7% (15/66) vs. 6.5% (3/46), χ(2) = 5.278, P < 0.05). Klebsiella pneumoniae was more common isolate in preterm infants than in term infants (13.0% (3/23) vs. 1.1% (1/89), χ(2) = 7.540, P < 0.05). Streptococcus (most were Streptococcus agalactiae) was the most common bacteria in early onset meningitis and higher than those in late onset meningitis (35.0% (7/20) vs. 12.0% (11/92), χ(2) = 4.872, P < 0.05). Drug sensitivity tests showed that all the Gram-positive bacterial isolates were sensitive to linezolid. Staphylococci were resistant to penicillin, and most of them were resistant to erythromycin, oxacillin and cefazolin; 77.8%of CNS isolates were methicillin-resistant staphylococcus. No Streptococcus and Enterococcus faecalis was resistant to penicillin. None of enterococci was resistant to vancomycin. Among the Gram-negative bacterial isolates, more than 40% of Escherichia coli were resistant to commonly used cephalosporins such as cefuroxime, cefotaxime and ceftazidime, and all of them were sensitive to amikacin, cefoperazone sulbactam and imipenem. Isolates of Klebsiella pneumoniae were all resistant to ampicillin, cefuroxime, cefotaxime and ceftazidime, but none of them was resistant to piperacillin tazobactam and imipenem. Of the 112 patients, 69 were cured, 23 improved, 9 uncured and 11 died. There were 47 cases (42.0%) with poor prognosis, they had abnormal head imageology, severe complications and some cases died, 13 of 18 (72.2%) patients with meningitis caused by Streptococcus died. CONCLUSION:Escherichia coli, CNS and Streptococcus are the predominant pathogens responsible for neonatal purulent meningitis over the past ten years. There were increasing numbers of cases with Streptococcus meningitis which are more common in early onset meningitis with adverse outcome, therefore careful attention should be paid in clinic. Linezolid should be used as a new choice in intractable neonatal purulent meningitis cases caused by gram positive bacteria.
    [Clinical analysis of children with group B meningitis in 2013-2017 in a single center]. Zhang X X,Geng Z X,Zhu L,Li M H,Wang Y J,Qian S Y,Liu G Zhonghua er ke za zhi = Chinese journal of pediatrics To explore the clinical features, the risk factors of mortality and drug resistance of the isolates in patients with group B (GBS) meningitis. A retrospective analysis was performed in 96 children with GBS meningitis (46 males and 50 females) at Beijing Children's Hospital Affiliated to Capital Medical University from January 2013 to October 2017. The clinical characteristics, prognosis and drug resistance were reviewed and analyzed. According to the onset time, the patients were divided into early onset disease (EOD, 0-6 days), late onset disease (LOD, 7-89 days) and very late onset disease (VLOD, 90 days-16 years), the clinical features were compared. According to the results of cranial imaging examination, the patients were divided into two groups: those with neurological complications and those without neurological complications. The influencing factors of neurological complications were analyzed. According to the outcome of 28 days after discharge, patients were divided into death group and survival group. The risk factors of mortality were analyzed by multivariate Logistic regression analysis. Non-numeric variables were analyzed with χ(2) test or Fisher's exact test. Numeric variable between groups were compared with nonparametric test. A total of 96 patients were enrolled, including 18 (19%) EOD, 71 (74%) LOD and 7 (7%) VLOD cases. The median age of EOD cases was 2 days, with a range from 0 to 6 days. The median age of LOD cases was 31 days, with a range from 7 to 81 days. The median age of VLOD cases was 153 days, with a range from 95 to 214 days. Before the onset of the disease, the mother had mastitis in 6 cases and premature rupture of membranes in 6 cases. The common clinical manifestations of patients were fever (95%, 91/96), anorexia (65%, 62/96), seizure (56%, 54/96), and consciousness changes (36%, 35/96). The differences were statistically significant in gender (13/18 28/71 5/7, χ(2)=7.705, 0.024), the number of cases who was admitted to intensive care unit (ICU) (5/18 31/71 0, χ(2)=6.065, 0.042) and peripheral blood leukocyte (12(4, 18)×10(9)/L 6(3, 11)×10(9)/L 13(6, 17)×10(9)/L, =9.885, 0.007) in EOD group, LOD group and VLOD group. Cranial imaging was performed in 94 patients, 60 patients (64%) developed neurological complications, including subdural effusion (31/94, 33%), followed by intracranial hemorrhage (26/94, 28%), cerebral softening (19/94, 20%), cerebral atrophy (15/94, 16%), ependinitis (8/94, 9%) and hydrocephalus (4/94, 4%). By univariate χ(2) test analysis, seizure (63% (38/60) 41% (14/34), χ(2)=4.310, 0.038) was a risk factor of neurological complications. Within 28 days after discharge, 88 patients survived and 8 patients died, with a fatality rate of 8%. The independent risk factors for the death were septic shock (: 9.548, 95% 1.439-63.356, 0.019) and respiratory failure (: 7.053, 95% 1.160-42.888, 0.034). All of isolates were susceptible to penicillin (68/68), ceftriaxone (47/47), cefepime (50/50), vancomycin (60/60) and linezolid (54/54), while the rates of resistance to tetracycline, levofloxacin, clindamycin and erythromycin were 5/12, 17/45, 38/46 and 32/37, respectively. The main type of GBS meningitis is late onset cases. The incidence of neurological complications was high. The independent risk factors for death were septic shock and respiratory failure. The strains were severely resistant to clindamycin and erythromycin. 10.3760/cma.j.issn.0578-1310.2019.06.010
    Prevalence and antibiotic resistance profiles of cerebrospinal fluid pathogens in children with acute bacterial meningitis in Yunnan province, China, 2012-2015. Jiang Hongchao,Su Min,Kui Liyue,Huang Hailin,Qiu Lijuan,Li Li,Ma Jing,Du Tingyi,Fan Mao,Sun Qiangming,Liu Xiaomei PloS one Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis. 10.1371/journal.pone.0180161
    Clinical and pathogenic analysis of 507 children with bacterial meningitis in Beijing, 2010-2014. Guo Ling-Yun,Zhang Zhi-Xiao,Wang Xi,Zhang Ping-Ping,Shi Wei,Yao Kai-Hu,Liu Lin-Lin,Liu Gang,Yang Yong-Hong International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases OBJECTIVES:To explore the clinical characteristics and analyze the pathogens of bacterial meningitis in children. METHODS:Bacterial meningitis cases occurring from January 2010 through December 2014 at Beijing Children's Hospital were reviewed retrospectively. The records of all patients, including data on clinical features and laboratory information, were obtained and analyzed. RESULTS:In total, the cases of 507 pediatric patients seen over a 5-year period were analyzed; 220 of these cases were etiologically confirmed. These patients were classified into four age groups: 29 days to 1 year (n=373, 73.6%), 1-3 years (n=61, 12.0%), 3-6 years (n=41, 8.1%), and >6 years (n=32, 6.3%). The main pathogens identified in this study were Streptococcus pneumoniae (n=73, 33.2%), Escherichia coli (n=24, 10.9%), Enterococcus (n=22, 10.0%), and group B Streptococcus (n=18, 8.2%). All Gram-positive bacteria were sensitive to vancomycin and linezolid. All Gram-negative bacteria were sensitive to meropenem. The total non-susceptibility rate of S. pneumoniae to penicillin was 47.6% (20/42). The resistance rates to ceftriaxone, cefepime, and ceftazidime were 75% (9/12), 55.6% (5/9), and 40% (4/10), respectively. CONCLUSIONS:The main pathogen of bacterial meningitis in this study was S. pneumoniae. The antibiotic resistance rates among children with bacterial meningitis are of serious concern. 10.1016/j.ijid.2016.07.010
    Glycopeptide insensitive Staphylococcus aureus subdural empyema treated with linezolid and rifampicin. Gallagher R M,Pizer B,Ellison J A,Riordan F A I The Journal of infection A 4-year-old boy had surgical debulking of a cerebral astrocytoma followed by chemotherapy. He developed a subdural empyema with a teicoplanin and methicillin resistant Staphylococcus aureus. He was successfully treated with surgical drainage and 6 weeks of antibiotic therapy which included linezolid, rifampicin and metronidazole. Linezolid may be successful in treating other CNS infections caused by antibiotic resistant gram-positive organisms. 10.1016/j.jinf.2008.06.023
    Linezolid for treatment of subdural empyema due to Streptococcus: case reports. Lefebvre Laurent,Metellus Philippe,Dufour Henry,Bruder Nicolas Surgical neurology BACKGROUND:Recurring subdural empyema despite adequate surgical drainage and antibiotic treatment is still a life-threatening disease. This is mainly due to poor diffusion of the antibiotic into the subdural space. CASE DESCRIPTION:We report 2 cases of recurring subdural empyema due to Streptococcus, after repeat surgery and high-dose antibiotic treatment including beta-lactamines and vancomycin. Both patients showed marked clinical and radiologic improvement after introduction of linezolid. There was no drug-related adverse effect despite 36 and 90 days of treatment. CONCLUSION:Off-label use of linezolid for treatment of subdural empyema due to gram-positive bacteria should be considered after failure of conventional antibiotic treatment. 10.1016/j.surneu.2007.06.083
    Successful treatment with linezolid of meningitis complicated with subdural empyema in a 6-month-old boy. Dinleyici Ener Cagri,Yarar Coskun,Dinleyici Meltem,Yakut Ayten Journal of tropical pediatrics Recent findings have focused on the possible role of linezolid as a suitable candidate for the treatment of central nervous system infections. The linezolid treatment for meningitis was sporadically reported in adults but there was no report in children. Here, we present a 6-month-old boy with meningitis and subdural empyema which was unresponsive to more conventional agents but successfully treated with linezolid therapy. A previously healthy 6-month-old boy was referred to our clinic for deteriorating general condition with fever, vomiting and seizures. He had fever and tense-bulging anterior fontanelle. Based on his first cerebrospinal fluid (CSF) results, empirical antibiotic therapy for bacterial meningitis consisting of vancomycin and ceftriaxone was started. However, CSF culture yielded no micro-organisms but blood culture showed coagulase-negative Staphylococci. On the 7th day, he still had high fever and the erythrocyte sedimentation rate (ESR) and serum CRP levels had risen by 105 mm/h and 36.2 mg/dl, respectively. On 10th day, computerized cranial tomography showed bilateral frontoparietal subdural empyema. Purulent material was evacuated by burr hole, and gram stains of the material showed polymorphonuclear leukocytes and no microorganisms. Clinical and CSF findings of our case were, unresponsiveness to vancomycin, ceftriaxone and consecutive meropenem treatment while we still observed subdural empyema during these treatments. For this reason we started linezolid 10 mg/kg twice daily. Clinical signs improved dramatically, with both completely normal neurological findings and normalization of CSF and radiological findings. To the of our best knowledge, linezolid treatment of meningitis in children has not been reported previously. Clinical and CSF findings of our case were improved completely with linezolid treatment. Also, control cranial computerized tomography showed the total recovery of subdural empyema. Here we present the youngest case with meningitis which was successfully treated with linezolid treatment. 10.1093/tropej/fmm058
    Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Saha Samir K,Darmstadt Gary L,Yamanaka Noboru,Billal Dewan S,Nasreen Tania,Islam Maksuda,Hamer Davidson H The Pediatric infectious disease journal BACKGROUND:Streptococcus pneumoniae is the leading cause of childhood pneumonia and meningitis worldwide. Isolation of this organism, however, is uncommon in resource-poor countries, in part because of extensive use of prior antibiotics. A rapid, highly sensitive immunochromatographic test (ICT) for S. pneumoniae was evaluated for the diagnosis of meningitis. METHODS:Cerebrospinal fluid (CSF) from 450 children with suspected meningitis was tested with ICT, and results were compared with CSF culture, latex agglutination test (LAT) and/or polymerase chain reaction (PCR). Serial CSF specimens from 11 patients were also evaluated for duration of positive results during effective antimicrobial therapy. FINDINGS:All 122 cases of pyogenic pneumococcal meningitis positive either by culture (N = 87) or PCR (N = 35) were positive by ICT, yielding 100% (122 of 122) sensitivity. All purulent CSF specimens from patients with meningitis caused by other bacteria by culture (N = 149) or by LAT (N = 48) or those negative by culture, LAT and LytA and thus of unknown etiology (N = 20), and normal CSF specimens (N = 104) were negative by ICT. Thus the specificity of ICT also was 100% (321 of 321), although negativity of ICT was not confirmed by PCR, if it was positive for other organisms either by culture or LAT. Serotyping of S. pneumoniae strains revealed 28 different serotypes, indicating that outcome of ICT are independent of diverse capsular serotype of pneumococcus. Antigen was detected by ICT for at least 10 days after presentation, and 1 was still positive on day 20, which was longer than for either LAT or PCR. INTERPRETATION:ICT for pneumococcal antigen in CSF is 100% sensitive and specific in diagnosing pyogenic pneumococcal meningitis and can detect approximately 30% more pneumococcal meningitis cases than with culture alone. The simplicity of the test procedure and the longevity of CSF antigen detection suggest the potential utility of ICT to estimate the true burden of pneumococcal disease, as for Haemophilus influenzae type b using data from meningitis, and to guide selection of appropriate antibiotic treatment, especially in resource-poor countries with widespread prehospital antimicrobial use.
    [Significance of soluble DLL1 in diagnosis of intracranial infectious diseases in children]. Li Jin-Yi,Jia Yan-Jie,Jia Yong-Lin,Lu Jing-Jing,Jing Li-Jun,Peng Tao,Li Jing-Hong Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To investigate the significance of soluble DLL1 (Delta-like-1) levels of cerebrospinal fluid (CSF) and serum in the diagnosis of intracranial infection in children. METHODS:Fifty children with intracranial infection, including 20 cases of tuberculous meningitis (TM), 20 cases of viral meningitis (VM) and 10 cases of purulent meningitis (PM), and 20 children without intracranial infection (control group) were enrolled. The levels of soluble DLL1 in CSF and serum were measured using ELISA. RESULTS:The level of CSF soluble DLL1 in the TM group was significantly higher than that in the VM, PM and control groups (2.89 ± 1.72 ng/mL vs 0.14 ± 0.14 ng/mL, 0.27 ± 0.21 ng/mL, 0.13 ± 0.12 ng/mL; P<0.01). The level of serum soluble DLL1 in the TM group was also significantly higher than that in the VM, PM and control groups (12.61 ± 6.45 ng/mL vs 2.28 ± 2.27 ng/mL, 2.38 ± 1.79 ng/mL, 2.26 ± 2.10 ng/mL; P<0.01). The levels of soluble DLL1 in the CSF and serum in the VM and PM groups were not significantly different from those in the control group. CONCLUSIONS:Soluble DLL1 as a novel indicator might have potentially important value in the diagnosis of TM.
    Subdural empyema in children. Muzumdar Dattatraya,Biyani Naresh,Deopujari Chandrashekhar Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery BACKGROUND:Subdural empyema denotes the collection of purulent material in the subdural spaceand is commonly seen in infants and older children. In infants, the most common cause is bacterialmeningitis. In older children, sinusitis and otitis media are usually the source for subdural empyema. Theclinical symptomatology is varied and has a wide range including prolonged or recurrent fever, seizures,meningeal irritation, and raised intracranial pressure. It can mimic as well as complicate meningitis and aheightened clinical awareness is therefore paramount. AIMS AND OBJECTIVES:The clinical profile, etiopathogenesis, imaging features and management of subdural empyema in children is discussed and the relevant literature is reviewed. CONCLUSION:Subdural empyema is a neurosurgical emergency and rapid recognition and treatment canavoid life-threatening complications. In most cases, surgical decompression through burr hole or craniotomyis warranted. Near complete evacuation of the purulent material and appropriate long-term intravenous antibiotics are necessary for a gratifying outcome. 10.1007/s00381-018-3907-6
    Evaluation of brainstem auditory evoked response audiometry findings in children with tuberculous meningitis at admission. Topcu Ismail,Cüreoğlu Sebahattin,Yaramiş Ahmet,Tekin Muhammet,Oktay Faruk,Osma Ustün,Meric Faruk,Katar Selahattin Auris, nasus, larynx OBJECTIVE:To determine the characteristics of Brainstem auditory evoked response (BAER) findings in children with tuberculous meningitis (TBM) at admission. METHODS:Twenty-seven children with highly probable TBM were admitted to the University Hospital. The control group was 23 healthy, age and sex matched subjects. Brainstem response audiometry recording was performed in all patients and controls. Ninety dB sound pressure level (SPL) was used for comparisons. The main BAER measurements analysed were the I-III, III-V, I-V interpeak intervals. In statistical analysis, t-test for independent groups were performed. At the same time, for interpeak intervals, values exceeding 2.5 standard deviations (S.D.) above the means of the normal controls were considered abnormal. To the result of BAER findings, HL was classified as mild (until 40 dBHL), severe (until 80 dBHL) and total HL (no hearing was detected). RESULTS:The latencies of interpeak intervals (except III-V latency at 10 per s) have significantly prolonged in comparison with controls. Mild HL was detected in four ears. In eight ears, any wave form could not be obtained at 110 dBSPL. Abnormal BAER result was seen in 13 of 54 ears (24%) at the click of 10 per s and five ears (12%) at the click of 50 per s. CONCLUSION:Abnormal BAER result was seen in 24% of patients with TBM before treatment. Depending on these findings, it can be inferred that hearing impairments must be lower than those values which was detected by BAER during the acute phase of TBM, since the abnormal BAER may be reversible following the illness, returning to normal with recovery.
    Outcome of brain stem auditory electrophysiology in children who survive purulent meningitis. Jiang Z D The Annals of otology, rhinology, and laryngology Brain stem auditory electrophysiology was assessed in children long after purulent meningitis by examining the central components of brain stem auditory evoked response (BAER) at different presentation rates of clicks. Children with peripheral hearing loss were excluded from this study to avoid any possible influence of the loss on the measurements of BAER central components. Of the 70 children who had recovered from meningitis 2 to 8 years earlier, 9 (12.9%) showed abnormalities in BAER central components--mainly a slight reduction of wave V amplitude, at the click presentation rate of 10/s. Of the remaining 61 children who did not show any obvious abnormalities in the BAER at 10/s, an abnormally prolonged I-V interval and a reduced amplitude of wave V were seen in 5 children (8.2%) at the click rate of 90/s. The total BAER abnormality rate was therefore 20.0% (14/70 cases). The results suggest that most children who survive purulent meningitis have a favorable outcome for the brain stem auditory pathway, with about 1 in 5 having mild dysfunction or a suboptimal outcome in the pathway. 10.1177/000348949910800502
    [Complications of purulent meningoencephalitis in children]. Rubin A N,Shcherbuk Yu A,Lyapin A P Vestnik khirurgii imeni I. I. Grekova An analysis of 19 cases of meningoencephalitis was made in infants aged under one year old. The disease was complicated by chronic subdural hematomas in 11 patients and by hydrocephalus in 8 patients. The article presents the strategy, treatment results and diagnostic procedures volume. Based on their work, the authors made a conclusion that meningoencephalitis required an emergency neurosurgical interference in order to avoid complications in convalescence period.
    Anti-interleukin-8 auto-antibodies in cerebrospinal fluid of children with purulent meningitis. Takasaki J,Ogawa Y Pediatrics international : official journal of the Japan Pediatric Society BACKGROUND:Cerebrospinal fluid (CSF) of patients with purulent meningitis contains a high concentration of interleukin (IL)-8. Recently, the presence of anti-IL-8 auto-antibodies was noted in blood and alveolar fluid. Therefore, measurement of the concentration of anti-IL-8 auto-antibodies was attempted in CSF of children with and without meningitis. METHODS AND RESULTS:We measured the concentration of anti-IL-8 auto-antibodies in CSF of children with purulent or aseptic meningitis and those without meningitis. The CSF obtained on admission showed a significantly higher concentration of anti-IL-8 IgG and IgM auto-antibodies in children with purulent meningitis, compared with those with aseptic meningitis or without meningitis. Among the three groups of children, the concentration of IL-8 was also significantly higher in CSF of children with purulent meningitis. CONCLUSION:Because the anti-IL-8 IgG auto-antibody binds to IL-8 and inhibits IL-8 interaction with specific receptors on neutrophils, the presence of anti-IL-8 auto-antibodies seems to provide a mechanism that limits the bioavailability of free IL-8 in CSF. 10.1046/j.1442-200x.2000.01198.x
    Characteristics of brain stem auditory evoked potentials in children with hearing impairment due to infectious diseases. Ječmenica Jovana Radovan,Opančina Aleksandra Aleksandar Bajec Journal of child neurology Among objective audiologic tests, the most important were tests of brain stem auditory evoked potentials. The objective of the study was to test the configuration, degree of hearing loss, and response characteristics of auditory brain stem evoked potentials in children with hearing loss occurred due to infectious disease. A case control study design was used. The study group consisted of 54 patients referred for a hearing test because of infectious diseases caused by other agents or that occurred as congenital infection. Infectious agents have led to the emergence of various forms of sensorineural hearing loss. We have found deviations from the normal values of absolute and interwave latencies in some children in our group. We found that in the group of children who had the diseases such as purulent meningitis, or were born with rubella virus and cytomegalovirus infection, a retrocochlear damage was present in children with and without cochlear damage. 10.1177/0883073814536467
    [First experience with detecting bacterial DNA in the cerebrospinal fluid of patients with purulent meningitis using broad spectrum multiplex nested PCR]. Moravcová Lenka,Pícha Dusan,Zdárský Emanuel,Holecková Daniela,Dzupová Olga,Lásiková Sárka Klinicka mikrobiologie a infekcni lekarstvi OBJECTIVES:To propose and verify a PCR assay for detecting Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Staphylococcus species, Streptococcus pneumoniae and Neisseria meningitidis serogroups B and C in a single sample of the cerebrospinal fluid of patients with purulent meningitis. MATERIAL AND METHODS:DNA from the cerebrospinal fluid was isolated using the QIAamp DNA Mini Kit. PCR was performed as two-step amplification (nested PCR). For E. coli, H. influenzae, L. monocytogenes, S. species and S. pneumoniae, universal and species-specific primers encoding bacterial 16S rDNA were used in the first and second reaction, respectively. For N. meningitidis serogroups B and C, an amplification system with primers for the SiaD gene was utilized. RESULTS:Of 25 patients examined at the beginning of their treatment, bacterial DNA was detected in the cerebrospinal fluid of 17 (68 %) of them. Those were six cases of N. meningitidis serogroup B, four of N. meningitidis serogroup C, five of S. pneumoniae, one of H. influenzae and one of L. monocytogenes. Of 7 patients in whom antibiotic therapy was initiated prior to diagnostic lumbar puncture, PCR was positive in four cases. CONCLUSIONS:The proposed nested PCR approach is faster than traditional culture methods and suitable for early laboratory diagnosis of infectious agents. When compared to culture methods, the technique offers slightly higher positivity (by 16 %). This is similar in samples analyzed after the initiation of antibiotic therapy. The PCR method never detected other bacteria than the cultured ones.
    Cranial computed tomography in purulent meningitis of childhood. Tuncer Oguz,Caksen Hüseyin,Arslan Sükrü,Atas Bülent,Uner Abdurrahman,Oner Ahmet Faik,Odabas Dursun The International journal of neuroscience The cranial computed tomography (CT) findings of 48 children with purulent meningitis were examined, prospectively, to determine the importance of cranial CT findings on the prognosis of childhood meningitis, in a developing country. The age of children ranged from 2 months to 13 years. Of 48 patients, 29 (60.5%) survived without sequelae, 13 (27%) survived with sequelae, and six (12.5%) died. Cranial CT was normal in 21 (43%) patients of 48 children with meningitis at admission. Abnormal CT findings were detected in 10, 11, and 6 children in the groups of survived without sequelae, survived with sequelae, and deaths, respectively, at admission (p <.05) We found that CT scan results were correlated with neurological signs (p <.05). At least one or more cranial CTs were was re-taken in children in whom the first CT revealed abnormal findings; we did not find a statistically significant difference for the follow-up CT findings between the groups (p >.05). Hydrocephalus and subdural effusion were the commonest abnormal CT findings. In conclusion, our findings showed that cranial CT may safely be used to detect intracranial complications of meningitis in childhood and the ratio of sequelae and death were more common in children with abnormal cranial CT than those of normal cranial CT findings. Additionally, there was a positive correlation between CT scan results and neurological signs. 10.1080/00207450490269435
    Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Ostergaard Christian,Benfield Thomas,Lundgren Jens D,Eugen-Olsen Jesper Scandinavian journal of infectious diseases The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent meningitis, 63 had lymphocytic meningitis, 12 had encephalitis, and 54 patients were suspected of, but had no evidence of, meningitis. There was a significant difference in suPAR levels among patient groups (Kruskal Wallis test, p < 0.0001) with significantly higher CSF suPAR levels in patients with CNS infection (purulent meningitis: median suPAR 2.41 microg/l (range 0.12-35), lymphocytic meningitis: 1.10 microg/l (0.15-5.31), and encephalitis (1.77 microg/l (0.17-11.7)) than in patients without meningitis (0.64 microg/l (0-5.34) (Dunn's multiple comparison test, p < 0.05). Also, patients with purulent meningitis had significantly higher CSF suPAR levels than patients with lymphocytic meningitis (p < 0.001). Patients with purulent meningitis who died (n = 8, 4.9 microg/l (1.3-35) had significantly higher CSF levels of suPAR than patients who survived (n = 46, 2.1 microg/l (0.1-24), Mann Whitney, p = 0.046). Employing a cut-off point of 3.1 and above, the OR (95%CI) for fatal outcome was 11.9 (1.4-106), univariate logistic regression analysis, p = 0.026. In conclusion, CSF suPAR levels may be an important predictor for fatal outcome in purulent meningitis.
    [An analysis of 181 cases with blood stream infection caused by Streptococcus agalactiae in children from 2011 to 2015: a multi-center retrospective study]. Hua C Z,Yu H,Zhuang J Q,Li X L,Xu H M,Luo Q E,Lu H P,Yu H M,Cao Y,Chen Y P,Zhang T,Jing C M,Du L Z,Wang C Q,Lin Z L,Zhang H,Chen X J,Hua Z Y Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To analyze the clinical characteristics of blood stream infection caused by Streptococcus agalactiae in children and the drug-resistance of the isolates. METHOD:All cases with Streptococcus agalactiae growth in blood or cerebrospinal fluid cultures from January 1, 2011 to December 31, 2015 were enrolled by checking the laboratory information system (LIS) from 7 Class 3 Grade A hospitals (4 in Zhejiang, 2 in Shanghai and 1 in Chongqing). Clinical data were collected for analysis. χ(2) test, t test and non parametric test were used in the study. RESULT:One hundred and eighty-one pediatric cases of blood stream infection caused by Streptococcus agalactiae were included in current study. Eighty-six cases (47.5%) were male, and with age range from one day to 9 years (media 13 days). Thirty cases (16.6%) were premature infants and 127 cases (70.2%) were born via vaginal delivery. Seventy-one cases (39.2%) had early onset (<7 d) infections, and 106 cases (58.6%) had late onset (7-89 d) infections. Seventy-eight cases (43.1%) were complicated with purulent meningitis. Incidences of vaginal delivery(81.7%(58/71) vs. 62.3%(66/106)), shortness of breath moaning (43.7%(31/71) vs. 15.1%(16/106)) and preterm premature rupture of membranes (25.4%(18/71) vs. 3.8%(4/106)) were higher in the early onset infection group compared with the late onset group(P all<0.05). However, the number of cases who had fever(25.4%(18/71)vs.85.8%(91/106)) and complicated with purulent meningitis (29.6%(21/71) vs. 53.8%(57/106)) in early onset infections group was less than that in the late onset group(P both<0.05). The blood cultures of most patients (87.8%) were performed before the use of antibiotics. Drug-resistant tests showed that the sensitive rates to penicillin G, ceftriaxone and cefotaxime were 98.9%, 99.0% and 99.0% respectively. All strains were sensitive to vancomucine. The rates of resistance to clindamycin and erythromycin were 68.0% and 34.0%, respectively. Only 39 cases (22.0%) were treated with single antibiotics of either penicillins or cephalosporins, 80 cases (45.2%) were treated with antibiotics containing β lactamase inhibitor, 61 cases (34.5%) were treated with either meropenem or cefoperazone-sulbactam. One hundred and fifty-four cases were cured, while 19 died (including 13 complicated with purulent meningitis) and 8 lost to follow up after giving up of treatment. CONCLUSION:The incidence and mortality of blood stream infection caused by Streptococcus agalactiae complicated with purulent meningitis are high in children. Penicillin is the first choice in treatment. Antibiotics should be selected accorrding to the drug-resistance test. 10.3760/cma.j.issn.0578-1310.2016.08.004
    Diagnostic Yield of Pneumococcal Antigen Detection in Cerebrospinal Fluid for Diagnosis of Pneumococcal Meningitis Among Children in China. Xie Yong-Ping,Hua Chun-Zhen,Wang Hong-Jiao,Sun An-Na,Shen Jue Indian pediatrics OBJECTIVE:To determine the diagnostic accuracy of pneumococcal antigen detection in diagnosis of pneumococcal meningitis in children. METHODS:Purulent meningitis was diagnosed according to European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guideline between July 2014 and June 2016. Along with a cerebrospinal fluid (CSF) culture, pneumococcal antigen detection in cerebrospinal fluid (CSF) was performed, and further identification of pathogens was done with 16S rDNA-PCR and high-throughput sequencing. RESULTS:CSF samples collected from 184 children (median age of 1.92 mo). CSF culture was used as the gold standard. 46 (25%) had positive results for culture and 10 (5.4%) were pneumococci; 34 (18.5%) were pneumococcal antigen positive. The sensitivity and specificity of pneumococcal antigen detection were 100% (95% CI: 89.4%-100%) and 86.2% (95% CI: 96.4%-99.9%), respectively. 92.3% (12/13) were confirmed by nucleic acid detection to be pneumococci. CONCLUSIONS:Pneumococcal antigen detection in CSF has adequate sensitivity and specificity in diagnosing pneumococcal meningitis.
    [Analysis by questionnaire survey concerning example such as purulent meningitis and severe infectious diseases--relation among patient background factor, sequelae, and infecting organism]. Sunakawa Keisuke The Japanese journal of antibiotics Concerning major causative organisms of purulent meningitis, i. e., Haemophilus influenzae and Streptococcus pneumoniae, a questionnaire was sent to medical institutions all over Japan with the aim of investigating the patient background factors, sequelae and causal relationship with the causative organisms. Responses from 84 institutions in various parts of Japan were summarized and the following conclusions were drawn. 1. The diagnostic names of 227 patients for whom the questionnaire could be recollected were as follows: Purulent meningitis 138 cases (patient under 15 years old; 134 cases); purulent meningitis and sepsis, 58 cases; sepsis, 28 cases; and others, 3 cases. The causative organisms for the patients with meningitis and meningitis + sepsis were as follows: Haemophilus influenzae, 132 patients; and Streptococcus pneumoniae, 44 patients. 2. With respect to age distribution among the patients with meningitis and those with meningitis + sepsis, the number of the patients of the age younger than 1 year old was more than twice larger than that of one-year-old patients. The percentage of the cases in which sequelae remained was 35.9% among the cases caused by Streptococcus pneumoniae and 13.4% among the cases caused by Haemophilus influenzae. A significant difference was observed between the bacterial strains (p=0.0025). 3. The major initial symptoms observed were high fever, vomiting, consciousness disorder, drowsiness and poor sucking. The percentage of the patients with remaining sequelae was significantly high among the patients who exhibited convulsion in the early stage after the onset. 4. As to the relationship with administration of dexamethasone, sequelae remained in 40.0% (10/25) of the patients who did not receive dexamethasone, and 17.3% (23/133) of the patients who received the drug. The percentage of the patients with remaining sequelae was significantly low among the patients who received dexamethasone (p=0.0043).
    5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Molyneux Elizabeth,Nizami Shaikh Qamaruddin,Saha Samir,Huu Khanh Truong,Azam Matloob,Bhutta Zulfiqar Ahmad,Zaki Ramadan,Weber Martin Willi,Qazi Shamim Ahmad, Lancet (London, England) BACKGROUND:Bacterial meningitis is an important cause of morbidity and mortality in developing countries, but the duration of treatment is not well established. We aimed to compare the efficacy of 5 and 10 days of parenteral ceftriaxone for the treatment of bacterial meningitis in children. METHODS:We did a multicountry, double-blind, placebo-controlled, randomised equivalence study of 5 versus 10 days of treatment with ceftriaxone in children aged 2 months to 12 years with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis. Our study was done in ten paediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam. We randomly assigned children who were stable after 5 days of treatment, through site-balanced computer-generated allocation lists, to receive a further 5 days of ceftriaxone or placebo. Patients, their guardians, and staff were masked to study-group allocation. Our primary outcomes were bacteriological failure or relapse. Our analysis was per protocol. This study is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN38717320. FINDINGS:We included 1004 of 1027 children randomly assigned to study groups in our analyses; 496 received treatment with ceftriaxone for 5 days, and 508 for 10 days. In the 5-day treatment group, two children (one infected with HIV) had a relapse; there were no relapses in the 10-day treatment group and there were no bacteriological failures in either study group. Side-effects of antibiotic treatment were minor and similar in both groups. INTERPRETATION:In children beyond the neonatal age-group with purulent meningitis caused by S pneumoniae, H influenzae type b, or N meningitidis who are stable by day 5 of ceftriaxone treatment, the antibiotic can be safely discontinued. FUNDING:United States Agency for International Development. 10.1016/S0140-6736(11)60580-1
    High-throughput sequencing of 16S rDNA amplicons characterizes bacterial composition in cerebrospinal fluid samples from patients with purulent meningitis. Liu Aicui,Wang Chao,Liang Zhijuan,Zhou Zhi-Wei,Wang Lin,Ma Qiaoli,Wang Guowei,Zhou Shu-Feng,Wang Zhenhai Drug design, development and therapy Purulent meningitis (PM) is a severe infectious disease that is associated with high rates of morbidity and mortality. It has been recognized that bacterial infection is a major contributing factor to the pathogenesis of PM. However, there is a lack of information on the bacterial composition in PM, due to the low positive rate of cerebrospinal fluid bacterial culture. Herein, we aimed to discriminate and identify the main pathogens and bacterial composition in cerebrospinal fluid sample from PM patients using high-throughput sequencing approach. The cerebrospinal fluid samples were collected from 26 PM patients, and were determined as culture-negative samples. The polymerase chain reaction products of the hypervariable regions of 16S rDNA gene in these 26 samples of PM were sequenced using the 454 GS FLX system. The results showed that there were 71,440 pyrosequencing reads, of which, the predominant phyla were Proteobacteria and Firmicutes; and the predominant genera were Streptococcus, Acinetobacter, Pseudomonas, and Neisseria. The bacterial species in the cerebrospinal fluid were complex, with 61.5% of the samples presenting with mixed pathogens. A significant number of bacteria belonging to a known pathogenic potential was observed. The number of operational taxonomic units for individual samples ranged from six to 75 and there was a comparable difference in the species diversity that was calculated through alpha and beta diversity analysis. Collectively, the data show that high-throughput sequencing approach facilitates the characterization of the pathogens in cerebrospinal fluid and determine the abundance and the composition of bacteria in the cerebrospinal fluid samples of the PM patients, which may provide a better understanding of pathogens in PM and assist clinicians to make rational and effective therapeutic decisions. 10.2147/DDDT.S82728
    Ameliorative effects of ceftriaxone sodium combined with dexamethasone on infantile purulent meningitis and associated effects on brain-derived neurotrophic factor levels. Zeng Yiwen,Zhang Wei Experimental and therapeutic medicine The aim of the present study was to evaluate the role of ceftriaxone sodium combined with dexamethasone on the treatment of infant purulent meningitis (PM) and to measure brain-derived neurotrophic factor (BDNF) levels in children with PM. Of the 177 patients enrolled into the present study, 92 patients received ceftriaxone sodium+dexamethasone (combination group) and 85 patients received ceftriaxone sodium alone (monotherapy group). The time taken for the body temperature, peripheral blood (PB) and cerebrospinal fluid (CSF) white blood cell (WBC) counts to recover back to normal levels were compared between the two groups. In addition, changes in the CSF WBC counts, CSF protein and sugar concentrations, BDNF levels, effective treatment rates and incidence of adverse reactions three days before treatment (T1), after one week of treatment (T2) and after two weeks of treatment (T3) were compared between the two groups. In the combination group, the recovery time of body temperature, WBC counts in both PB and CSF were significantly lower compared with those in the monotherapy group. The combination group also exhibited lower CSF protein concentrations and higher CSF sugar concentrations at T2 and T3 compared with those in the monotherapy group (P<0.05). The effective treatment rate of the combination group was significantly higher compared with that of the monotherapy group (P=0.006). CSF protein at T1, T2 T3, and CSF sugar concentrations and BDNF levels at T1 were significantly lower in the combination group than in the monotherapy group (P<0.05) while the CSF sugar concentrations at T2, T3 were higher in the combination group than in the monotherapy group (P<0.05). Taken together, these observations suggest that ceftriaxone combined with dexamethasone was superior compared with that of ceftriaxone alone for the treatment of infantile PM, and that this combination therapy may improve the effective treatment rate and accelerate patient rehabilitation. 10.3892/etm.2020.8769
    [A multicentric clinical study on clinical characteristics and drug sensitivity of children with meningitis in China]. Wang C Y,Xu H M,Deng J K,Yu H,Chen Y P,Lin A W,Cao Q,Hao J H,Zhang T,Deng H L,Chen Y H Zhonghua er ke za zhi = Chinese journal of pediatrics To understand clinical characteristics of children with meningitis (PM) in China and to analyze the drug sensitivity of isolates and associated impacts on death and sequelae. The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis test were used for statistical analysis. There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count 12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in 3 years old group (25.0% (16/64) . 5.8% (3/52), 75.0% (48/64) . 25.0% (13/52), 48.4% (31/64) . 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; 0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in 3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) . 1.6%(1/64), 80.8% (42/52) . 48.4% (31/64), 69.2% (36/52) . 37.5% (24/64), 55.8% (29/52) . 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; 0.000, 0.000, 0.001, 0.000). isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, 0.031 and 0.002). The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem. 10.3760/cma.j.issn.0578-1310.2019.05.008
    [Risk factors associated with the development of early neurological complications in purulent meningitis in a pediatric population]. Espinoza-Oliva Martha Marcela,Rizo-Santos Dalia Berenice,Díaz-Peña Rafael,Ortega-Cortés Rosa,Barrera de León Juan Carlos Gaceta medica de Mexico OBJECTIVE:To determine the risk factors associated with the development of early neurological complications in purulent meningitis in a pediatric population. METHODS:This was a case-control study including 78 children aged one month to 16 years with purulent meningitis divided into two groups: cases, with early neurological complications (defined as those presenting < 72 hours from initiation of clinical manifestation), and controls, without early neurological complications. Clinical, serum laboratory, and cerebrospinal fluid (CSF). RESULTS:Seventy-eight patients were included: cases, n = 33, and controls, n = 45. Masculine gender, 19 (57%) vs. feminine gender, 28 (62%) (p = 0.679). Median age in months, 36 months (range, 1-180) vs. 12 months (range, 1-168) (p = 0.377). Factors associated with neurological complications: convulsive crises on admission, p = 0.038, OR, 2.65 (range, 1.04-6.74); meningeal signs, p = 0.032, OR, 2.73 (range, 1.07-6.96); alteration of the alert state, p = 0.003, OR, 13.0 (range, 1.64-105.3); orotracheal intubation, p = 0.000, OR, 14.47 (range, 4.76-44.01); neurological deterioration, p = 0.000, OR, 9.60 (range, 3.02-30.46); turbid CSF, p = 0.003, OR, 4.20 (range, 1.57-11.20); hypoglycorrhachia, < 30 mg/dl, p = 0.001, OR, 9.2 (range, 3.24-26.06); and positive CSF culture, p = 0.001, OR, 16.5 (range, 1.97-138.1). CONCLUSIONS:The factors associated with early neurological complications included convulsive crises on admission, meningeal signs, alteration of the alert state, need for orotracheal intubation, turbid CSF, hypoglycorrhachia, and positive CSF culture.
    Accuracy of cerebrospinal fluid ferritin for purulent meningitis. Garcia Pedro Celiny Ramos,Barcelos Andrea Lucia Machado,Tonial Cristian Tedesco,Fiori Humberto Holmer,Einloft Paulo Roberto,Costa Caroline Abud Drumond,Portela Janete L,Bruno Francisco,Branco Ricardo Garcia Archives of disease in childhood OBJECTIVE:To evaluate the use of cerebrospinal fluid (CSF) ferritin levels in the diagnosis of purulent meningitis (PM). METHOD:We studied 81 children between 28 days and 12 years of age who presented with clinical suspicion of meningitis to the emergency department. CSF ferritin levels were measured and compared between diagnostic groups (PM, aseptic meningitis (AM) and no meningitis). RESULTS:The median age was 24 (IQR 8-69) months. There were 32 patients with AM (39%), 23 with PM (28%) and 26 with no meningitis (32%). Median CSF ferritin was 4.2 ng/mL (IQR 3.0-6.5), 52.9 ng/mL (IQR 30.7-103 ng/mL) and 2.4 ng/mL (IQR 2-4), respectively. CSF ferritin was higher in children with PM compared with AM (p<0.001) or no meningitis (p<0.001). There was no difference between AM and no meningitis. CONCLUSION:CSF ferritin may be a useful biomarker to discriminate PM in children with clinical symptoms of this disease. 10.1136/archdischild-2019-317960
    [Clinical features of childhood purulent meningitis caused by Escherichia coli and Streptococcus pneumoniae: a comparative analysis]. Han Wei,Jiang Li,Ma Jian-Nan,Song Xiao-Jie,He Rong Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To investigate the differences in clinical features of childhood purulent meningitis (PM) caused by Escherichia coli and Streptococcus pneumoniae, and to provide help for the selection of antibiotics for PM children with unknown etiology. METHODS:A retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children). RESULTS:Compared with the Streptococcus pneumoniae infection group, the Escherichia coli infection group had a significantly higher proportion of children with an age of onset of <3 months and a significantly higher incidence rate of convulsion, but significantly lower incidence rates of severe fever (>39°C) and disturbance of consciousness and a significantly lower proportion of children with an increased leukocyte count at diagnosis (>12×10(9)/L). The results of routine cerebrospinal fluid test and biochemical examinations showed no significant differences between the two groups. Escherichia coli and Streptococcus pneumoniae were resistant to cephalosporins and had a sensitivity to chloramphenicol more than 90%. Escherichia coli was fully sensitive to meropenem and Streptococcus pneumoniae was fully sensitive to vancomycin. CONCLUSIONS:PM caused by Escherichia coli and Streptococcus pneumoniae has different clinical features. As for PM children with severe fever, disturbance of consciousness, and an increased leukocyte count, the probability of Streptococcus pneumoniae infection should be considered. For PM children with an age of onset of <3 months, medium- and low-grade fever, frequent convulsions, and a leukocyte count of <12×10(9)/L, the probability of Escherichia coli infection should be considered.
    Correlation between CD64 and PCT levels in cerebrospinal fluid and degree of hearing impairment sequelae in neonates with purulent meningitis. Liu Cui,Zhao Dongchi Experimental and therapeutic medicine This study investigated the possible correlation between the degree of hearing impairment caused by neonatal purulent meningitis and the levels of CD64 and PCT in cerebrospinal fluid of patients, and assessed the prognostic value of such levels. We recorded data from 156 cases of neonatal purulent meningitis retrospectively. All the patients received brainstem response audiometry, and cerebrospinal fluid samples were collected within the first day after admission through lumbar puncture. Flow cytometry was used to detect CD64 levels and enzyme-linked fluorescent assay was used to detect PCT levels. The children with hearing impairment were followed up for 1 year and brainstem response audiometry was performed again in them. We found that 43.59% of the children showed different degrees of hearing impairment, and 55% of them did not fully recover. The levels of PCT and CD64 in cerebrospinal fluid of children with hearing impairment were significantly higher than those of children with normal hearing (P<0.01). The levels of PCT and CD64 in mild, moderate and severe hearing impaired children increased gradually with higher degrees of impairment, and the differences between groups were significant (P<0.01). During the follow-up, it was found that the levels of PCT and CD64 in children correlated well with the degree of hearing recovery, and the differences between groups were significant (P<0.01). In our study, approximately 1/4 children with purulent meningitis showed long-term hearing impairment. Based on our analyses, the levels of CD64 and PCT in cerebrospinal fluid can be used to predict the degree and long-term prognosis of hearing impairment caused by purulent meningitis in children. 10.3892/etm.2017.5273
    Differential fatty acid analysis of cerebrospinal fluid in infants and young children with suspected meningitis. Ekhtiyari Elham,Barzegar Mohammad,Mehdizadeh Amir,Shaaker Maghsood,Ghodoosifar Sepideh,Abhari Alireza,Darabi Masoud Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery PURPOSE:Meningitis is relatively common in infants and young children and can cause permanent brain damage. The aim of this study was to determine whether meningitis is associated with fatty acids in cerebrospinal fluid (CSF). METHODS:CSF samples from children between 3 months and 6 years of age admitted to the Tabriz public hospitals who met clinical criteria of meningitis were collected at enrollment. A total of 81 samples were analyzed for fatty acid profile by gas-liquid chromatography. RESULTS:Children with a purulent meningitis demonstrated a higher percentage of oleic acid (p < 0.05, >10 %) and lower percentages of omega-3 polyunsaturated fatty acids (p < 0.001, <-40 %) than aseptic meningitis and nonmeningitis groups did. There was an inverse relationship between CSF long-chain omega-3 fatty acids and the total number of leukocytes and differential counts of neutrophils and lymphocytes in the purulent meningitis group. Moreover, significantly lower omega-3 fatty acids (p = 0.001, -37 %) and higher ratio of n-6/n-3 (p = 0.02, -29 %) were found in patients with purulent meningitis with sepsis than in those with meningitis and no sepsis. CONCLUSIONS:This study provides evidence that purulent meningitis and its complication with sepsis are associated with important disturbances in CSF fatty acids, mainly deficiency in long-chain omega-3 polyunsaturated fatty acids. 10.1007/s00381-016-3232-x
    [Clinical analysis of purulent meningitis in 317 children]. Xu Qing-Qing,Li Mei Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the clinical features, treatment, and prognosis of purulent meningitis (PM) in children. METHODS:A retrospective analysis was performed on the clinical data of 317 children with PM aged from 1 month to 15 years. RESULTS:PM was commonly seen in infants (198 cases, 62.6%). Most children with PM had preceding respiratory infection (171 cases, 53.9%). The major clinical manifestations of PM were fever, convulsions, and intracranial hypertension, and convulsions were more commonly seen in infants (152 cases, 93.6%). The major complication was subdural effusion (95 cases, 29.9%). Of the 95 cases of subdural effusion, 22 cases were diagnosed by subdural puncture; 68 cases underwent subdural puncture and 62 cases restored to normal temperature 3-5 days after puncture. Risk factors associated with complications and sequelae were young age and protein≥1 g/L in cerebrospinal fluid (CSF) (OR=0.518, 1.524 respectively; P<0.05). The third-generation cephalosporins were the first choice for PM, and vancomycin or carbapenems were replacement therapy. Thirteen (14.4%) out of 90 children had delayed cerebral vasculitis during a follow-up visit within 3 months after discharge. CONCLUSIONS:PM is more commonly seen in infants, and the infants have a high incidence of convulsions. Young age and protein≥1 g/L in CSF may increase the risk of complications and sequelae. Subdural puncture is not only a diagnostic method but also a therapy for subdural effusion. Some children have delayed cerebral vasculitis during a follow-up visit within 3 months after discharge, so follow-up visits should be performed within 3 months after discharge.
    Development of a TaqMan Array card to target 21 purulent meningitis-related pathogens. Zhao Chengna,Wang Xi,Zhang Chao,Liu Bing,Jing Hongbo,Ming Lihua,Jiang Hua,Zheng Yuling,Liu Peng,Liu Gang,Jiang Yongqiang BMC infectious diseases BACKGROUND:Purulent meningitis (PM) is a serious life-threatening infection of the central nervous system (CNS) by bacteria or fungi and associated with high mortality and high incidence of CNS sequelae in children. However, the conventional cerebrospinal fluid (CSF) culture method is time-consuming and has a low sensitivity. METHODS:Our study developed a real-time PCR-based purulent meningitis-TaqMan array card (PM-TAC) that targeted 21 PM-related pathogens and could produce results within 3 h. Primers and probes were adapted from published sources possibly. The performance of them were evaluated and optimized and then they were spotted on TAC. RESULTS:The PM-TAC showed a sensitivity and specificity of 95 and 96%, respectively. For all of the 21 targeted pathogens, the PM-TAC assay had a LOD ranging from 5 copies/reaction to 100 copies/reaction, an intra-assay variation of 0.07-4.45%, and an inter-assay variation of 0.11-6.81%. Of the 15 CSF samples collected from patients with PM after empiric antibiotic therapies, the positive rate was 53.3% (8/15) for our PM-TAC assay but was only 13.3% (2/15) for the CSF culture method. Of the 17 CSF samples showing negative CSF culture, the PM-TAC assay identified a case of Neisseria meningitidis infection. Furthermore, all of the 10 CSF samples from patients without CNS infection showed negative for the PM-TAC assay. CONCLUSIONS:Our PM-TAC assay also demonstrated that the pathogen loads in the CSF samples correlated with the severity of PM. Thus, the PM-TAC may be helpful to improve the prognosis of PM and clinical outcomes from antibiotic therapies. 10.1186/s12879-019-3856-z
    Rapid pathogen identification using a novel microarray-based assay with purulent meningitis in cerebrospinal fluid. Hou Yuting,Zhang Xu,Hou Xiaolin,Wu Ruofen,Wang Yanbai,He Xuexian,Wang Libin,Wang Zhenhai Scientific reports In order to improve the diagnosis of pathogenic bacteria in cerebrospinal fluid (CSF) with purulent meningitis, we developed a DNA microarray technique for simultaneous detection and identification of seven target bacterium. DNA were extracted from 24 CSF samples with purulent meningitis (or suspected purulent meningitis). The specific genes of each pathogen were chosen as the amplification target, performed the polymerase chain reaction (PCR), labeled with a fluorescence dye, and hybridized to the oligonucleotide probes on the microarray. There is no significant cross-hybridization fluorescent signal occurred in untargeted bacteria. There were 87.5% (21/24) positive results in DNA microarray compared with the 58.3% (14/24) of the CSF culture test. Of which 58.3% (14/24) of the patients with culture-confirmed purulent meningitis, 37.5% (9/24) patients who were not confirmed by culture test but were demonstrated by the clinical diagnosis and DNA microarray. Multiple bacterial infections were detected in 5 cases by the microarray. In addition, the number of gene copies was carried out to determine the sensitivity of this technique, which was shown to be 3.5 × 10 copies/μL. The results revealed that the microarray technique which target pathogens of the CSF specimen is better specificity, accuracy, and sensitivity than traditional culture method. The microarray method is an effective tool for rapidly detecting more target pathogens and identifying the subtypes of strains which can eliminate the impact of the different individuals with purulent meningitis for prompt diagnosis and treatment. 10.1038/s41598-018-34051-0
    Bacterial meningitis in Sudanese children; critical evaluation of the clinical decision using clinical prediction rules. Abdelrahim Nada Abdelghani,Fadl-Elmula Imad Mohammed,Ali Hassan Mohammed BMC pediatrics BACKGROUND:Sudan falls in the meningitis belt where most global cases of bacterial meningitis are reported. Highly accurate decision support tools have been developed by international specialized societies to guide the diagnosis and limit unnecessary hospital admissions and prolonged antibiotic use that have been frequently reported from countries around the world. The goals of this study are to critically evaluate the clinical decision of bacterial meningitis in children in Sudan using clinical prediction rules and to identify the current bacterial aetiology. METHODS:This cross-sectional hospital-based study was conducted in October to July of 2010 in a major referral pediatric hospital in Khartoum, Sudan. Febrile children age 1 day to 15 years who were provisionally diagnosed as having meningitis on admission were included (n = 503). Cerebrospinal fluid (CSF) specimens were obtained from all patients while clinical and demographic data were available for only 404. Conventional laboratory investigations were performed. The clinical decision was evaluated by the International Classification of Diseases-Clinical Modification code 320.9 and the Bacterial Meningitis Score. Ethical clearance and permissions were obtained. RESULTS:Out of 503 provisionally diagnosed bacterial meningitis patients, the final clinical confirmation was assigned to 55.9%. When codes were applied; 5.7% (23/404) with CSF pleocytosis were re-classified as High Risk for bacterial meningitis and 1.5% (6/404) with confirmed bacterial aetiology as Proven Bacterial Meningitis. Neisseria meningitidis was identified in 0.7% (3/404) and Streptococcus pneumoniae in another 0.7%. Typical laboratory findings (i.e. CSF pleocytosis and/or low glucose and high protein concentrations, Gram positive or Gram negative diplococcic, positive bacterial culture) were seen in 5 (83%). Clinically, patients showed fever, seizures, chills, headache, vomiting, stiff neck and bulging fontanelle. All confirmed cases were less than 5 years old and were admitted in summer. All patients were prescribed with antibiotics; they were all recovered and discharged. CONCLUSIONS:Bacterial meningitis is over-diagnosed in hospitals in Khartoum therefore clinical prediction rules must be adopted and applied to guide the clinical decision. The sole bacterial aetiology in this selected group of Sudanese children remain N. meningitidis and S. pneumoniae, but with significant decrease in prevalence. Some cases showed atypical clinical and laboratory findings. 10.1186/s12887-019-1684-3
    How many single-nucleotide polymorphisms (SNPs) must be tested in order to prove susceptibility to bacterial meningitis in children? Analysis of 11 SNPs in seven genes involved in the immune response and their effect on the susceptibility to bacterial meningitis in children. Gowin Ewelina,Świątek-Kościelna Bogna,Kałużna Ewelina,Strauss Ewa,Wysocki Jacek,Nowak Jerzy,Michalak Michał,Januszkiewicz-Lewandowska Danuta Innate immunity The aim of this study is to describe the prevalence of single single-nucleotide polymorphisms (SNPs) as well as their combinations in genes encoding proteins involved in the immune response in children with bacterial meningitis. The prospective study group consisted of 39 children with bacterial meningitis and 49 family members surveyed between 2012 and 2016. Eleven SNPs in seven genes involved in immune response were analysed. The mean number of minor frequency alleles (MAF) of studied SNPs was lowest in the control group and highest in patients with pneumococcal meningitis. We found that carrying ≥6 MAF of studied SNPs was associated with an increased risk of pneumococcal meningitis. The prevalence of risky variants was noted to be higher in patients with pneumococcal meningitis as compared to the control group. In conclusion, genetic factors are a relevant factor in determining the susceptibility to bacterial meningitis. A statistically significant cumulative effect of mutated variants on increasing the risk of bacterial meningitis was detected. Combining all three SNPs in MBL2 improves the prediction of susceptibility to pneumococcal meningitis. Analysis of risky alleles can help indicate people prone to the disease who are 'gene-immunocompromised'. 10.1177/1753425918762038
    Etiology of Bacterial Meningitis Among Children <5 Years Old in Côte d'Ivoire: Findings of Hospital-based Surveillance Before and After Pneumococcal Conjugate Vaccine Introduction. Boni-Cisse Catherine,Jarju Sheikh,Bancroft Rowan E,Lepri Nicaise A,Kone Hamidou,Kofi N'zue,Britoh-Mlan Alice,Zaba Flore Sandrine,Usuf Effua,Ndow Peter Sylvanus,Worwui Archibald,Mwenda Jason M,Biey Joseph N,Ntsama Bernard,Kwambana-Adams Brenda A,Antonio Martin Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Bacterial meningitis remains a major disease affecting children in Côte d'Ivoire. Thus, with support from the World Health Organization (WHO), Côte d'Ivoire has implemented pediatric bacterial meningitis (PBM) surveillance at 2 sentinel hospitals in Abidjan, targeting the main causes of PBM: Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus). Herein we describe the epidemiological characteristics of PBM observed in Côte d'Ivoire during 2010-2016. METHODS:Cerebrospinal fluid (CSF) was collected from children aged <5 years admitted to the Abobo General Hospital or University Hospital Center Yopougon with suspected meningitis. Microbiology and polymerase chain reaction (PCR) techniques were used to detect the presence of pathogens in CSF. Where possible, serotyping/grouping was performed to determine the specific causative agents. RESULTS:Overall, 2762 cases of suspected meningitis were reported, with CSF from 39.2% (1083/2762) of patients analyzed at the WHO regional reference laboratory in The Gambia. In total, 82 (3.0% [82/2762]) CSF samples were positive for bacterial meningitis. Pneumococcus was the main pathogen responsible for PBM, accounting for 69.5% (52/82) of positive cases. Pneumococcal conjugate vaccine serotypes 5, 18C, 19F, and 6A/B were identified post-vaccine introduction. Emergence of H. influenzae nontypeable meningitis was observed after H. influenzae type b vaccine introduction. CONCLUSIONS:Despite widespread use and high coverage of conjugate vaccines, pneumococcal vaccine serotypes and H. influenzae type b remain associated with bacterial meningitis among children aged <5 years in Côte d'Ivoire. This reinforces the need for enhanced surveillance for vaccine-preventable diseases to determine the prevalence of bacterial meningitis and vaccine impact across the country. 10.1093/cid/ciz475
    Vitamin D was not associated with survival or cerebrospinal fluid cathelicidin levels in children with bacterial meningitis. Savonius Okko,Pelkonen Tuula,Roine Irmeli,Viljakainen Heli,Andersson Sture,Fernandez Josefina,Peltola Heikki,Helve Otto Acta paediatrica (Oslo, Norway : 1992) AIM:Vitamin D deficiency impairs the immunological system and has been associated with worse outcomes of infectious diseases, but its role in bacterial meningitis remains unknown. We investigated whether serum 25-hydroxyvitamin D concentrations related to disease outcomes and to cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis. METHODS:All consecutively enrolled patients in a clinical trial on childhood bacterial meningitis in Latin America in 1996-2003 were considered, and 142 children, with a median age of seven months who had a confirmed bacterial aetiology and frozen serum available for further analyses, were included in this study. Serum 25-hydroxyvitamin D concentrations were determined with a chemiluminescence immunoassay analyser, while CSF cathelicidin was measured by enzyme-linked immunosorbent assay. RESULTS:The median serum 25-hydroxyvitamin D concentration was 96 (range 19-251) nmol/L. No relationship was found with patient survival, but children with any neurological sequelae had lower serum 25-hydroxyvitamin D levels than children without sequelae. Serum 25-hydroxyvitamin D was unrelated to cathelicidin concentrations in CSF. CONCLUSION:Although serum 25-hydroxyvitamin D in children with bacterial meningitis was not associated with survival or CSF cathelicidin concentrations, its relationship with more detailed disease outcomes warrants further study. 10.1111/apa.14393
    Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo. Tsolenyanu Enyonam,Bancroft Rowan E,Sesay Abdul K,Senghore Madikay,Fiawoo Mawouto,Akolly Djatougbe,Godonou Mawussi A,Tsogbale Novissi,Tigossou Segla D,Tientcheu Leopold,Dagnra Anoumou,Atakouma Yawo,Sylvanus Ndow Peter,Worwui Archibald,Landoh Dadja E,Mwenda Jason M,Biey Joseph N,Ntsama Bernard,Kwambana-Adams Brenda A,Antonio Martin Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. METHODS:Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction. RESULTS:Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2-5 years. CONCLUSIONS:Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo. 10.1093/cid/ciz473