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Subacute and chronic meningitis (SCM) presents significant diagnostic challenges, with numerous infectious and non-infectious inflammatory causes. This study examined patients aged 16 and older with SCM admitted to referral centers for neuroinfections and neuroinflammations in Mashhad, Iran, between March 2015 and October 2022. Among 183 episodes, tuberculous meningitis was the most common infectious cause (46.5%), followed by Brucella meningitis (24.6%). The cause of SCM was definitively proven in 40.4%, presumptive in 35.0%, and unknown in 24.6% of cases. In-hospital mortality was 14.4%, and 30.5% of survivors experienced unfavorable outcomes (Glasgow Outcome Scale 2-4). Patients with unknown causes had a significantly higher risk of death compared to those with presumptive or proven diagnoses (risk ratio 4.18). This study emphasizes the diagnostic difficulties of SCM, with one-quarter of cases remaining undiagnosed and over one-third having only a presumptive diagnosis. Improving diagnostic methods could potentially enhance prognosis and reduce mortality.

Objectives: To summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children., Methods: This was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests)., Results: Seventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups., Conclusion: AB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ye, Fu, Wu, Xu, Ye, Han, Wang and Yu.)

Background: Otitis is commonly associated with community-acquired bacterial meningitis, but the role of ear surgery as treatment is debated. In this study, we investigated the impact of otitis and ear surgery on outcome of adults with community-acquired bacterial meningitis., Methods: We analyzed episodes of adults with community-acquired bacterial meningitis from a nationwide prospective cohort study in the Netherlands, between March 2006 and July 2021., Results: A total of 2548 episodes of community-acquired bacterial meningitis were evaluated. Otitis was present in 696 episodes (27%). In these patients the primary causative pathogen was Streptococcus pneumoniae (615 of 696 [88%]), followed by Streptococcus pyogenes (5%) and Haemophilus influenzae (4%). In 519 of 632 otitis episodes (82%) an ear-nose-throat specialist was consulted, and surgery was performed in 287 of 519 (55%). The types of surgery performed were myringotomy with ventilation tube insertion in 110 of 287 episodes (38%), mastoidectomy in 103 of 287 (36%), and myringotomy alone in 74 of 287 (26%). Unfavorable outcome occurred in 210 of 696 episodes (30%) and in 65 of 696 episodes was fatal (9%). Otitis was associated with a favorable outcome in a multivariable analysis (odds ratio 0.74; 95% confidence interval [CI] .59-.92; P = .008). There was no association between outcome and ear surgery., Conclusions: Otitis is a common focus of infection in community-acquired bacterial meningitis in adults, with S. pneumoniae being the most common causative pathogen. Presence of otitis is associated with a favorable outcome. Ear surgery's impact on the outcome of otogenic meningitis patients remains uncertain., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Context: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear., Objectives: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes., Data Sources: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials., Study Selection: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes., Data Extraction: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence., Results: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes., Conclusions: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.

Background: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited., Purpose: To gain a better understanding about GAS meningitis., Methods: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized., Results: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%., Conclusions: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death., (© 2024. The Author(s).)

Importance: The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain., Objective: To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis., Data Sources: Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality., Study Selection: Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded., Data Extraction and Synthesis: Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used., Main Outcome and Measure: Case fatality ratios of bacterial meningitis., Results: This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001)., Conclusions and Relevance: In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.

Objective: To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019., Methods: Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density., Results: 182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted., Conclusion: A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I 2  = 90.1%, 95% CI 71.9-98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180-362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28-4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03-3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital., (© 2022. The Author(s).)

Our objective was to quantify the differences in the outcomes from childhood bacterial meningitis (BM) and to describe the factors associated with them in different parts of the world. This study is a secondary analysis of prospectively collected data from five clinical BM trials conducted in Finland, Latin America (LatAm), and Angola between 1984 and 2017. As all data were collected uniformly, direct comparison of the series was possible. Associations between patient characteristics and death or dismal outcome-the triad of death, severe neurological sequelae, or deafness-were explored. In all, data on 2123 children with BM were analyzed. Etiology was confirmed in 95%, 83%, and 64%, in Finland, LatAm and Angola, respectively. The leading agents were Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Dismal outcome was the end result for 54%, 31%, and 5% of children in Angola, LatAm, and Finland, respectively. Although underweight, anemia, and tardy arrival worsened prognoses in Angola and LatAm, it was the presenting condition that was central in terms of outcome. In multivariate analysis, the factors independently associated with dismal outcome were the study site (Angola vs. Finland, OR 11.91, 95% CI 5.54-25.63, p < 0.0001 or LatAm vs. Finland, OR 9.46, 95% CI 4.35-20.61, p < 0.0001), Glasgow Coma Score < 13 (OR 4.58, 95% CI 3.31-6.32, p < 0.0001), seizures (OR 1.96, 95% CI 1.43-2.69), age < 1 year (OR 1.55, 95% CI 1.13-2.14, p = 0.007), and pneumococcal etiology (OR 1.49, 95% CI 1.08-2.06, p = 0.015). Greatly dissimilar outcomes from BM reflected the findings on admission on all three continents. Optimizing growth, preventing anemia, and prompt treatment may improve outcomes in resource poor areas., (© 2021. The Author(s).)

Background: Studies evaluating the epidemiology of pediatric meningitis are limited in our region. This study aimed to describe recent trends in the incidence of pediatric meningitis., Methods: We estimated national trends in hospitalization rates for pediatric meningitis (<18 years) by analyzing data from the Health Insurance Review and Assessment database between 2010 and 2018. Meningitis cases were identified based on International Classification of Diseases, Tenth Revision (ICD-10) codes and hospitalization rates were calculated., Results: In this national population-based study, a total of 119,644 hospitalizations and 58 deaths due to pediatric meningitis were identified. The hospitalization rates of pediatric bacterial meningitis have declined by 50.0%, from 3.4 per 100,000 in 2010 to 1.7 per 100,000 in 2018. The mortality rates for bacterial and viral meningitis were 2.0% and 0.002%, respectively. Despite the decreased annual incidence of bacterial meningitis, its mortality rate did not change significantly during the study period. The only risk factor identified for mortality in bacterial meningitis patients among age group, sex, region of residence, and season was age below 1 year (P < 0.001). As children under 1 year have a high-mortality rate (4.2%), patients in this age group require close monitoring. The reasons behind indistinct seasonal patterns of bacterial meningitis warrant further investigation., Conclusions: Childhood bacterial meningitis has shown a significant decline in incidence from 2010 to 2018. In contrast, viral meningitis has not shown a trend over time. Knowledge of these changes may aid clinicians in the decision-making process and management of meningitis patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Bacterial meningitis is a neurological emergency with high morbidity and mortality. We herein investigated clinical features, etiology, antimicrobial susceptibility profiles, and prognosis of bacterial meningitis in adults from a single tertiary center. We retrospectively reviewed medical records of patients with laboratory-confirmed bacterial meningitis from 2007 to 2016. Patients with recent neurosurgery, head trauma, or indwelling neurosurgical devices were classified as having healthcare-related meningitis. Causative microorganisms were identified by analyzing cerebrospinal fluid (CSF) and blood cultures, and antimicrobial susceptibility profiles were evaluated. We performed multiple logistic regression analysis to identify factors associated with unfavorable outcomes. We identified 161 cases (age, 55.9 ± 15.5 years; male, 50.9%), of which 43 had community-acquired and 118 had healthcare-related meningitis. CSF and blood culture positivity rates were 91.3% and 30.4%, respectively. In community-acquired meningitis patients, Klebsiella pneumoniae (25.6%) was the most common isolate, followed by Streptococcus pneumoniae (18.6%) and Listeria monocytogenes (11.6%). The susceptibility rates of K. pneumoniae to ceftriaxone, cefepime, and meropenem were 85.7%, 81.3%, and 100%, respectively. Among healthcare-related meningitis patients, the most common bacterial isolates were coagulase-negative staphylococci (28.0%), followed by Staphylococcus aureus (16.1%) and Enterobacter spp. (13.6%). Neurological complications occurred in 39.1% of the patients and the 3-month mortality rate was 14.8%. After adjusting for covariates, unfavorable outcome was significantly associated with old age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.06), neurological complications (OR 4.53, 95% CI 1.57-13.05), and initial Glasgow coma scale ≤ 8 (OR 19.71, 95% CI 4.35-89.40). Understanding bacterial pathogens and their antibiotic susceptibility may help optimize antimicrobial therapy in adult bacterial meningitis.

Objectives: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM)., Methods: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed., Results: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/μL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001)., Conclusions: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis., Clinicaltrial: Gov identification number: NCT01730690., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM)., Methods: We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality., Results: We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p <  0.001) and more often had a Charlson comorbidity score of ≥3 (40% vs 15%, p <  0.001). Neck stiffness (56% vs 75%, p <  0.001), headache (41% vs 78%) p <  0.001), nausea and/or vomiting (32% vs 56% p < 0.001), and rash (12% vs 26%, p = 0.007) were less frequent in diabetics, whereas altered mental status was more common. Streptococcus pneumoniae and Listeria meningitis were the most common etiologic agents (24 and 18%, respectively). Listeria was more frequent (18% vs. 10%, p = 0.033), whereas meningococcal meningitis was less frequent (10% vs 32%, p < 0.001). Overall mortality was higher in patients with diabetes (26% vs 16%, p = 0.025) concerning non-diabetics., Conclusions: Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common, whereas Neisseria meningitidis is significantly less frequent than in non-diabetics.

Background: Few data on intracranial group A Streptococcus (GAS) infection in children are available. Here, we describe the demographic, clinical, and diagnostic characteristics of 91 children with intracranial GAS infection., Methods: Cases of intracranial GAS infection in persons ≤18 years of age reported between 1997 and 2014 were identified by the Centers for Disease Control and Prevention's population- and laboratory-based Active Bacterial Core surveillance (ABCs) system. Medical charts were abstracted using a active, standardized case report form. All available isolates were emm typed. US census data were used to calculate rates., Results: ABCs identified 2596 children with invasive GAS infection over an 18-year period; 91 (3.5%) had an intracranial infection. Intracranial infections were most frequent during the winter months and among children aged <1 year. The average annual incidence was 0.07 cases per 100000 children. For 83 patients for whom information for further classification was available, the principal clinical presentations included meningitis (35 [42%]), intracranial infection after otitis media, mastoiditis, or sinusitis (34 [41%]), and ventriculoperitoneal shunt infection (14 [17%]). Seven (8%) of these infections progressed to streptococcal toxic shock syndrome. The overall case fatality rate was 15%. GAS emm types 1 (31% of available isolates) and 12 (13% of available isolates) were most common., Conclusions: Pediatric intracranial (GAS) infections are uncommon but often severe. Risk factors for intracranial GAS infection include the presence of a ventriculoperitoneal shunt and contiguous infections in the middle ear or sinuses., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2018.)

Background: Death from bacterial meningitis is rarely attributed to the actual event causing death. The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis., Methods: In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown., Results: We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%)., Conclusion: Fatal complications due to the primary infection - meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.

Background: Pseudomonas aeruginosa neurosurgical meningitis is a rare entity, usually related with intraventricular catheters and associated with high mortality rates. We describe the clinical characteristics, treatment and outcomes of a series of neurosurgical meningitis caused by P. aeruginosa along 1990-2016., Methods: Descriptive, retrospective study of all postsurgical meningitis due to P. aeruginosa related to intraventricular catheters in Hospital Universitario Central de Asturias, between 1990 and 2016. Clinical features, therapeutic approaches and prognostic factors were analyzed statistically. A binary logistic regression analysis was performed to determine the factors influencing the infection mortality., Result: 51 episodes from 51 different patients with CSF culture positive for P. aeruginosa were reviewed. Seventeen patients (33.3%) died as a direct consequence of the infection. Univariate analysis showed that mortality was higher in the group of patients treated with ceftazidime (12 vs. 15, p=0.068, OR 3.040 [0.877-10.544]) and lower in patients whom had received intrathecal therapy (2 vs. 13, p=0.050, OR 4.64 [0.80-34.93]), without differences observed between those patients treated with aminoglycosides or with colistin. Any patient treated with colistin died (0 vs. 6, p=0.067, OR: not defined). In the multivariate analysis mortality was only significant higher for patients without catheter withdrawal (p=0.014) and lower for those patients who received intrathecal therapy (p=0.05) or adequate empirical treatment (p=0.006)., Conclusions: The mortality of P. aeruginosa meningitis is high especially in infections without catheter withdrawal and in patients for whom the intrathecal route of administration was not used. Catheter withdrawal was an independent factor of good outcome in our series., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background and Objective: Meningitis is a medical and public health problem in Morocco, particularly in the North West region. The purpose of present study was to identify the pathogen in pyogenic meningitis and to determine its antibiotic susceptibility pattern Materials and Methods: A total of 247 cases were included in the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF)., Results: The study included 247 cases with a mean cumulative incidence of 4.53 (100,000 Hts) meningitis in all forms during the study period. The sex ratio M/F was 1.71. Maximum numbers of cases were<15 year of age, 139 (56.3%). Bacterial meningeal syndrome was observed in 67.2% of cases. Cerebrospinal fluid (CSF) was cloudy in 57.1% of cases. The average number of GBs was 1074.12 (±2115.63) elements mm-3. Mean glycorrhachia was 0.48 g L-1 (±0.28) and mean protein levels were 1.5 g L-1 (±1.68). The common pathogens identified on CSF culture were coagulase, negative Neisseria meningitidis in 30 (13%) and Streptococcus pneumoniae 6 (2.5%). Overall mortality was 14.9%., Conclusion: Hence, Meningitis is a real health problem in the province of Kenitra, affecting especially children. Effective involvement of all health personnel and the community fight this epidemic disease.

Background: The complement system is a vital component of the inflammatory response occurring during bacterial meningitis. Blocking the complement system was shown to improve the outcome of experimental pneumococcal meningitis. Complement factor H (FH) is a complement regulatory protein inhibiting alternative pathway activation but is also exploited by the pneumococcus to prevent complement activation on its surface conferring serum resistance., Methods: In a nationwide prospective cohort study of 1009 episodes with community-acquired bacterial meningitis, we analyzed whether genetic variations in CFH influenced FH cerebrospinal fluid levels and/or disease severity. Subsequently, we analyzed the role of FH in our pneumococcal meningitis mouse model using FH knock-out (Cfh -/- ) mice and wild-type (wt) mice. Finally, we tested whether adjuvant treatment with human FH (hFH) improved outcome in a randomized investigator blinded trial in a pneumococcal meningitis mouse model., Results: We found the major allele (G) of single nucleotide polymorphism in CFH (rs6677604) to be associated with low FH cerebrospinal fluid concentration and increased mortality. In patients and mice with bacterial meningitis, FH concentrations were elevated during disease and Cfh -/- mice with pneumococcal meningitis had increased mortality compared to wild-type mice due to C3 depletion. Adjuvant treatment of wild-type mice with purified human FH led to complement inhibition but also increased bacterial outgrowth which resulted in similar disease outcomes., Conclusion: Low FH levels contribute to mortality in pneumococcal meningitis but adjuvant treatment with FH at a clinically relevant time point is not beneficial.

For longer than a century, the "meningitis belt" of sub-Saharan Africa has experienced the largest-ever global meningitis epidemic. Whereas HIV-associated immunosuppression drives higher susceptibility to environmental infectious organisms with tropism for the central nervous system (CNS), most diagnostic laboratories in the belt stick to  N. meningitidis , H. influenzae , and S. pneumoniae . Cryptococcus neoformans has been the leading cause of death (incidence, 89%; death, 75%). To establish whether diagnostic services target geographically important pathogens, there is a need to know the current spectrum of etiology. Given Africa's agro-silvo-pastoralism, the One Health diagnostic approach is recommended. Considering  multipathogen detection capacity, needed speed for corticosteroid therapy decision, and susceptibility/resistance to antimicrobials with improved CNS penetration, proposed laboratory categorization will help neurologists to choose suitable services.

Objective: Bacterial meningitis (BM) is associated with a high morbidity and mortality. Cerebrospinal fluid (CSF) lactate may be used as a prognostic marker of this condition. We hypothesized that CSF lactate levels would remain elevated in participants who died of acute BM compared with those who recovered from this disease. To evaluate the potential use of lactate and other CSF biomarkers as prognostic markers of acute BM outcome., Methods: This retrospective, longitudinal study evaluated dynamic CSF biomarkers in 223 CSF samples from 49 patients who fulfilled the inclusion criteria of acute BM, with bacteria identified by CSF culturing. The participants were grouped according to outcome: death (n = 9; 18.37%) and survival (n = 40; 81.63%). All participants received appropriate antibiotic treatment., Results: In the logistic regression model, lactate concentration in the final CSF sample, xanthochromia, and CSF glucose variation between the first and last CSF samples were predictors of a poor outcome (death). In contrast, decrease in CSF white blood cell count and CSF percentage of neutrophils, increase in the percentage of lymphocytes, and normalization of the CSF lactate concentration in the last CSF sample were predictors of a good prognosis., Conclusion: The study confirmed the initial hypothesis. The longitudinal analysis of CSF lactate is an important predictor of prognosis in acute BM.

Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22; P  = 0.79). The OR for 90-day mortality was 1.47 (CI, 0.62 to 3.52; P  = 0.38) and for unfavorable outcome was 1.10 (CI, 0.75 to 1.63; P  = 0.62). The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as an empirical treatment for the majority of patients with ABM., (Copyright © 2019 American Society for Microbiology.)

Background: Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana., Methods: Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis., Results: There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010-2012) to 40.0% (8 of 20) after its introduction (2013-2016)., Conclusions: Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM)., Methods: From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM., Results: A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively., Conclusions: Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Bacterial meningitis is a major cause of morbidity and mortality in sub-Saharan Africa. We analyzed data from the World Health Organization's (WHO) Invasive Bacterial Vaccine-preventable Diseases Surveillance Network (2011-2016) to describe the epidemiology of laboratory-confirmed Streptococcus pneumoniae (Spn), Neisseria meningitidis, and Haemophilus influenzae meningitis within the WHO African Region. We also evaluated declines in vaccine-type pneumococcal meningitis following pneumococcal conjugate vaccine (PCV) introduction., Methods: Reports of meningitis in children <5 years old from sentinel surveillance hospitals in 26 countries were classified as suspected, probable, or confirmed. Confirmed meningitis cases were analyzed by age group and subregion (South-East and West-Central). We described case fatality ratios (CFRs), pathogen distribution, and annual changes in serotype and serogroup, including changes in vaccine-type Spn meningitis following PCV introduction., Results: Among 49 844 reported meningitis cases, 1670 (3.3%) were laboratory-confirmed. Spn (1007/1670 [60.3%]) was the most commonly detected pathogen; vaccine-type Spn meningitis cases declined over time. CFR was the highest for Spn meningitis: 12.9% (46/357) in the South-East subregion and 30.9% (89/288) in the West-Central subregion. Meningitis caused by N. meningitidis was more common in West-Central than South-East Africa (321/954 [33.6%] vs 110/716 [15.4%]; P < .0001). Haemophilus influenzae (232/1670 [13.9%]) was the least prevalent organism., Conclusions: Spn was the most common cause of pediatric bacterial meningitis in the African region even after reported cases declined following PCV introduction. Sustaining robust surveillance is essential to monitor changes in pathogen distribution and to inform and guide vaccination policies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Bacterial meningitis is a major cause of mortality among children under 5 years of age. Senegal is part of World Health Organization-coordinated sentinel site surveillance for pediatric bacterial meningitis surveillance. We conducted this analysis to describe the epidemiology and etiology of bacterial meningitis among children less than 5 years in Senegal from 2010 and to 2016., Methods: Children who met the inclusion criteria for suspected meningitis at the Centre Hospitalier National d'Enfants Albert Royer, Senegal, from 2010 to 2016 were included. Cerebrospinal fluid specimens were collected from suspected cases examined by routine bacteriology and molecular assays. Serotyping, antimicrobial susceptibility testing, and whole-genome sequencing were performed., Results: A total of 1013 children were admitted with suspected meningitis during the surveillance period. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus accounted for 66% (76/115), 25% (29/115), and 9% (10/115) of all confirmed cases, respectively. Most of the suspected cases (63%; 639/1013) and laboratory-confirmed (57%; 66/115) cases occurred during the first year of life. Pneumococcal meningitis case fatality rate was 6-fold higher than that of meningococcal meningitis (28% vs 5%). The predominant pneumococcal lineage causing meningitis was sequence type 618 (n = 7), commonly found among serotype 1 isolates. An ST 2174 lineage that included serotypes 19A and 23F was resistant to trimethoprim-sulfamethoxazole., Conclusions: There has been a decline in pneumococcal meningitis post-pneumococcal conjugate vaccine introduction in Senegal. However, disease caused by pathogens covered by vaccines in widespread use still persists. There is need for continued effective monitoring of vaccine-preventable meningitis., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Suppurative meningitis-meningoencephalitis (M-ME) is a sporadic disease in neonatal ungulates and only a few studies have reported the involvement of Streptococcus bovis/Streptococcus equinus complex (SBSEC) members in bovine neonatal M-ME. The SBSEC taxonomy was recent revised and previous biotype II/2 was reclassified as S. gallolyticus subsp. pasteurianus (SGP). The aim of this study was to describe a case of fatal neonatal neurological syndrome associated with SGP in calves. Ten calves were monitored because of neurological hyperacute symptoms associate with bilateral hypopyon and death. They were not fed with maternal colostrum; two of them died and were subjected to bacteriological, histopathological and biomolecular analysis as well as antibiotic susceptibility test. Both animals presented lesions mostly concentrated to meninges and brain and had bilateral hypopyon. Nine strains isolated in purity from brain, ocular humors and colon were identified as S. bovis group by using the API Strep system and as S. gallolyticus by using the 16S rRNA sequence. Two of these strains where subjected to WGS analysis that confirmed the sub-species identification and the clonality of the two SGP strains. The strains were found resistant to OT, SXT, MTZ and EN and susceptible to AMP, AMC, KZ and CN. We hypothesized that the syndrome observed could be due to the lack of maternal colostrum feeding. A timely and precise diagnosis could have likely prevented the death of the calves and, since the zoonotic potential of SBSECs members is known, accurate and rapid identification is required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To explore the clinical features, the risk factors of mortality and drug resistance of the isolates in patients with group B streptococcus (GBS) meningitis. Methods: 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. Results: 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 vs. 28/71 vs. 5/7, χ(2)=7.705, P= 0.024), the number of cases who was admitted to intensive care unit (ICU) (5/18 vs. 31/71 vs. 0, χ(2)=6.065, P= 0.042) and peripheral blood leukocyte (12(4, 18)×10(9)/L vs. 6(3, 11)×10(9)/L vs. 13(6, 17)×10(9)/L, H =9.885, P= 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) vs. 41% (14/34), χ(2)=4.310, P= 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 ( OR : 9.548, 95% CI 1.439-63.356, P= 0.019) and respiratory failure ( OR : 7.053, 95% CI 1.160-42.888, P= 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. Conclusions: 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.

Objectives: To evaluate the Full Outline of Unresponsiveness (FOUR) score as a predictor of outcome in adult patients with bacterial meningitis., Methods: We selected 427 patients from a nationwide, prospective cohort on community-acquired bacterial meningitis included from August 2011 to November 2016. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected. We compare the FOUR score with the Glasgow Coma Scale (GCS) score, performed a receiver operator characteristic curve analysis, and calculated the area under the curve (AUC) of the FOUR and GCS scores for the prediction of unfavorable outcome and mortality., Results: The median FOUR score on admission was 14 (interquartile range [IQR] 12-16), and the median GCS score was 12 (IQR 9-14). The outcome was unfavorable in 135 of 427 (32%) patients, of whom 55 (13%) died. There was a strong correlation between the FOUR score and the GCS score ( r = 0.85, p < 0.001). AUCs for the GCS and FOUR scores in the prediction of unfavorable outcome (both 0.64) and mortality (both 0.68) were comparable. Logistic regression analysis showed that the FOUR motor, brainstem, and respiration items were individual predictors of unfavorable outcome and mortality. For the GCS score, only the motor component was predictive, while the FOUR score provided a spectrum of clinical abnormalities in patients with a GCS score of 3., Conclusions: The FOUR score adds considerably to the prediction of outcome in patients with severe meningitis by means of better testing of the brainstem reflexes and respiration status. Future studies should consider incorporating the FOUR score into clinical assessment., (© 2019 American Academy of Neurology.)

Background: Staphylococcus aureus meningitis is an uncommon nosocomial infection usually associated with neurosurgical procedures, but spontaneous infections may occasionally appear., Aims: To compare the features of meningitis caused by meticillin-resistant (MRSA) and meticillin-susceptible (MSSA) S. aureus and examine the prognostic factors for mortality, including MRSA infection and combined antimicrobial therapy., Methods: Retrospective cohort study of 350 adults with S. aureus meningitis admitted to 11 hospitals in Spain (1981-2015). Logistic regression and propensity score matching were used to analyse prognostic factors., Results: There were 118 patients (34%) with MRSA and 232 (66%) with MSSA. Postoperative infection (91% vs 73%) and nosocomial acquisition (93% vs 74%) were significantly more frequent in MRSA than in MSSA meningitis (P < 0.001). Combined therapy was given to 118 (34%) patients. Overall 30-day mortality rate was 23%. On multivariate analysis, mortality was associated with severe sepsis or shock (odds ratio (OR) 9.9, 95% confidence interval (CI) 4.5-22.0, P < 0.001), spontaneous meningitis (OR 4.2, 95% CI 1.9-9.1, P < 0.001), McCabe-Jackson score rapidly or ultimately fatal (OR 2.8, 95% CI 1.4-5.4, P = 0.002), MRSA infection (OR 2.6, 95% CI 1.3-5.3, P = 0.006), and coma (OR 2.6, 95% CI 1.1-6.1, P < 0.029). In postoperative cases, mortality was related to retention of cerebrospinal devices (OR 7.9, 95% CI 3.1-20.3, P < 0.001)., Conclusions: Clinical and epidemiological differences between MRSA and MSSA meningitis may be explained by the different pathogenesis of postoperative and spontaneous infection. In addition to the severity of meningitis and underlying diseases, MRSA infection was associated with increased mortality. Combined antimicrobial therapy was not associated with increased survival., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Despite advances in neonatal intensive care and the improvements in surveillance, prevention and vaccination programs, neonatal meningitis still represents an important cause of morbidity and mortality in infants, with the highest mortality in the newborn population. The aim of this article was to summarize current knowledge about this topic with particular attention to management of neonatal meningitis in order to provide a useful tool for clinicians., Evidence Acquisition: We reviewed the existent literature from five European Countries (France, German, Italy, Spain and UK) on the effectiveness of treatments for bacterial meningitis in newborns taking into consideration the antibiotic resistance phenomenon., Evidence Synthesis: There are few data available on this topic; bacterial neonatal meningitis treatment and management is currently based more on experience than on high quality evidences., Conclusions: Identification of the knowledge gaps may stimulate researchers to design new studies aiming to better define management strategies of bacterial meningitis in newborns.

Objectives: To assess meningitis treatment in Lebanon's compatibility with the Infectious Diseases Society of America (IDSA) guidelines and the effect of non-compliance on mortality. Methods: This is a retrospective study, conducted in 5 Lebanese hospitals, and enrolling all patients diagnosed with meningitis who presented to the involved hospitals from January 2008 to December 2016.  Results: A total of 252 participants were enrolled in the study. Of these patients, 205 (82.7%) were diagnosed with viral meningitis and 47 (17.3%) with bacterial meningitis, which was confirmed using laboratory tests. For patients with viral meningitis, 128 (62.4%) remained on the initial prescribed antibiotics despite the negative cerebrospinal fluid (CSF) and blood culture results. For bacterial meningitis patients, 30.8% received treatment regimen incompatible with the IDSA guidelines. The most common reason for the treatment incompatibility was the definitive drug choice after the culture results (49.1%) and the least common reason was inappropriate hospital stay days (25.9%). The mortality rate was 13.5%. Having low proteins values in the CSF (odds ratio=0.095) was associated with lower mortality compared to patients with normal protein values. Conclusion: This study shows a high percentage of inappropriate treatment in Lebanese hospitals despite these hospitals having adopted international treatment guidelines. This inappropriate management was associated with an increasing rate of mortality and neurological complications.

Objective: To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis)., Study Design: Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt., Results: Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths., Conclusions: Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Community acquired bacterial meningitis (CABM) is responsible for high mortality and disabling sequelae. Introduction of pneumococcal conjugate vaccine (PCV-10) and haemophilus influenzea type b (Hib) has changed the epidemiological and clinical features of patients presenting with CABM as it is shown in different literatures over the last decade. The aim of this study was to assess the clinical and epidemiologic features and outcomes of CABM after the introduction of PCV-10 in Gondar University Hospital (GUH)., Methods: This is a retrospective study among children between 2 months and 14 years of age discharged from Gondar University Hospital. All patient records discharged with a diagnosis of meningitis at GUH were reviewed from September 2011 - September 2013. The data was collected using a structured questionnaire from the patient record charts and analysis was done using SPSS-20., Results: 80 cases (1.6%) of CABM out of 4996 admissions were identified. There were 60 (75%) cases of CABM using WHO criteria of cerebrospinal fluid leukocytosis (CSF) > 100cells/mm 3 , or 10-100cells/mm 3 with either hypoglycorrhea or increased protein; and 20 (25%) with culture confirmation. S. Pneumoniae was the most frequent pathogen identified in 14 (70%) children. The most common age group were infants 2-12 month old (n = 32, 40%). Children with adverse outcomes had shown a higher frequency of being older children (p = 0.045), loss of consciousness (p = 0.046), seizure at admission (p < 0.01), and a positive CSF culture (p = 0.03)., Conclusion: Introduction of PCV-10 has shown a decreased admission rate, mortality, and neurologic sequelae due to CABM., Competing Interests: The authors declare no competing interests.

Streptococcus pneumoniae continues to take a heavy toll on childhood mortality and morbidity across the developing world. An estimated 10.6 million invasive pneumococcal diseases (IPDs) occur every year, with nearly 1 million deaths in children under 5 years of age. Introduction of vaccines in the childhood immunisation programme in developed world has brought down the incidence of the disease considerably. However, childhood immunocompromising illnesses including HIV have increased the risk of IPD several folds. There is also a growing concern on the increasing antibiotic resistance among these invasive strains to penicillin, other beta-lactams and macrolides, making treatment difficult and expensive. It is estimated that about 62% of IPD worldwide is caused by the 10 most common serotypes. Although the ranking of individual pneumococcal serotypes causing serious disease varies among nations, the 7-13 serotypes included in pneumococcal conjugate vaccines (PCVs) may prevent 50%-80% of all paediatric pneumococcal diseases globally. The World Health Organization has recommended the use of PCV-10/13 in the national immunisation programmes (NIPs) of developing countries. Four doses of PCV-13 have been recommended by the US Association of Pediatrics and Centers for Disease Control and Prevention, at intervals of each 2 months for the first 6 months and by the 12 th to 15 th months after birth. This is expected to reduce the morbidity and mortality associated with IPD and simultaneously decrease colonisation with circulating antibiotic-resistant strains in immunized communities. Nevertheless, continued surveillance of antimicrobial resistance in non-vaccine serotypes is necessary to prevent the resurgence of resistance. Other virulence factors which are not serotype specific also need to be studied to overcome the drawbacks of serotype-specific pneumococcal vaccines. PCV-13 was launched during May 2017 under the NIP of five Indian states with the highest pneumococcal diseases in the country and is expected to be rolled out in the other parts of the country in the coming days., Competing Interests: None

Background: The mortality of neonatal pyogenic meningitis is reduced to 10-15%, but morbidity is unchanged., Methods: Primary objective is to determine the outcome, i.e. death or abnormal neurological examination (NE) at discharge and abnormal developmental quotient (DQ) at 3 months. Secondary objective is to find predictors of poor outcome., Results: In all, 89 neonates enrolled, 10 expired and 24 neonates had abnormal NE at discharge. A total of 59 neonates came for follow up, 13 had DQ < 70. Prolonged shock (odds ratio, OR: 8.28; p = 0.001), coma (OR: 4.3; p = 0.001), seizures (OR: 14; p = 0.012), mechanical ventilation (OR: 18.55; p = 0.00), orogastric feeding (OR: 2.78; p = 0.042) and electroencephalography (EEG; OR: 9.6; p = 0.00) predicted poor short-term outcome. Abnormal NE at discharge (OR: 15.6; p = 0.001), EEG (OR = 10.60; p = 0.00) and brainstem-evoked reflex audiometry (OR = 37.20, p = 0.00) predicted a low DQ at 3 months. Mortality and morbidity of neonates with Pyogenic Meningitis (PM) were similar to that in developed countries. Outcome depended on severity of the disease and NE at discharge.

The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. The 14-day, 30-day and in-hospital mortality rates were nominally lower for patients who received ITH/IVT colistin adjunctive therapy versus patients who received only IV colistin (24% vs. 38%, 29% vs. 56% and 29% vs. 56%, respectively). The costs of treatment were significantly lower, the lengths of hospital and intensive care unit (ICU) stay were significantly shorter, and the number of ventilator days was significantly less among patients who received ITH/IVT colistin compared with patients who did not receive ITH/IVT colistin. The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08-1.46) and 0.77 (0.44-0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: To investigate prognostic factors among critically ill patients with community-acquired bacterial meningitis and acute kidney injury., Methods: A retrospective study including patients admitted to a tertiary infectious disease hospital in Fortaleza, Brazil diagnosed with community-acquired bacterial meningitis complicated with acute kidney injury. Factors associated with death, mechanical ventilation and use of vasopressors were investigated., Results: Forty-one patients were included, with a mean age of 41.6 ± 15.5 years; 56% were males. Mean time between intensive care unit admission and acute kidney injury diagnosis was 5.8 ± 10.6 days. Overall mortality was 53.7%. According to KDIGO criteria, 10 patients were classified as stage 1 (24.4%), 18 as stage 2 (43.9%) and 13 as stage 3 (31.7%). KDIGO 3 significantly increased mortality (OR = 6.67; 95%CI = 1.23 - 36.23; p = 0.028). Thrombocytopenia was not associated with higher mortality, but it was a risk factor for KDIGO 3 (OR = 5.67; 95%CI = 1.25 - 25.61; p = 0.024) and for mechanical ventilation (OR = 6.25; 95%CI = 1.33 - 29.37; p = 0.02). Patients who needed mechanical ventilation by 48 hours from acute kidney injury diagnosis had higher urea (44.6 versus 74mg/dL, p = 0.039) and sodium (138.6 versus 144.1mEq/L; p = 0.036)., Conclusion: Mortality among critically ill patients with community-acquired bacterial meningitis and acute kidney injury is high. Acute kidney injury severity was associated with even higher mortality. Thrombocytopenia was associated with severer acute kidney injury. Higher urea was an earlier predictor of severer acute kidney injury than was creatinine.

Background: Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013., Objectives: To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability., Search Methods: We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015)., Selection Criteria: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis., Data Collection and Analysis: Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence., Main Results: We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence)., Authors' Conclusions: Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Objectives: To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM)., Methods: We conducted a chart review of all adults with proven CABM in three centres in Denmark from 1998 through to 2014. Patients were categorized as early diagnosis of CABM immediately on admission, or late diagnosis if CABM was not listed in referral or admission records and neither lumbar puncture nor antibiotic therapy for meningitis was considered immediately on admission. We used modified Poisson regression analysis to compute adjusted relative risks with 95% CIs for predictors of late diagnosis and in-hospital mortality., Results: A total of 113/358 (32%) patients were categorized as late diagnosis demonstrating a variety of tentative diagnoses of which 81/113 (72%) were non-infectious. We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%), concomitant pneumonia (26/113, 23% versus 26/245, 11%), and meningococcal meningitis (6/113, 5% versus 52/245, 21%). These variables remained statistically significant in multivariate analysis. Moreover, late diagnosis was associated with increased in-hospital mortality (41/113, 36% versus 43/245, 18%; adjusted relative risk 1.7, 95% CI 1.2-2.5)., Conclusions: Late diagnosis of CABM was common and patients were admitted with mostly non-infectious diagnoses. Absence of neck stiffness did not rule out CABM and special attention should be given to patients with pneumonia and the elderly. Late diagnosis was associated with incorrect patient management and increased mortality., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The current recommended therapies for bacterial meningitis are effective antimicrobial agents and the implementation of childhood vaccination programs. However, the role of adjunctive dexamethasone therapy in bacterial meningitis remains controversial., Methods: Using meta-analysis, this study aims to investigate the efficacy of adjunctive dexamethasone therapy in bacterial meningitis by comparing it with antibiotic therapy. Documents of randomized controlled trials (RCT) related to the treatment of bacterial meningitis in children with dexamethasone published since the establishment of the databases to December in 2016 were retrieved from the databases of Cochrane Library, Pubmed, MEDLINE, EMBASE, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure. The references in RCT were retrieved by hands at the same time. Full texts of screened documents were searched and given qualitative review, and then, all RCT included were analyzed statistically by using Review Manger 5.3 software., Results: The search yielded 15 studies (2409 children cases), among which 4 fall in grade A and 11 were grade B. The results of meta-analysis have shown that patients who received dexamethasone have significantly lower risks in incidence of hearing loss (OR = 0.68, 95%CI 0.53-0.89, P = 0.004) and severe neurological sequelae (OR = 0.59, 95%CI 0.37-0.95, P = 0.03), but the follow-up mortality is hardly effected (OR = 0.86, 95%CI 0.67-1.10, P = 0.23)., Conclusions: Evidence has proven that the adjunctive administration of dexamethasone is conducive to treating children with bacterial meningitis to a certain extent, to decreasing the possibility of hearing loss and severe neurological sequelae, but has no significant effect on the follow-up mortality.

Background: Early treatment is pivotal for favorable outcome in acute bacterial meningitis (ABM). Lumbar puncture (LP) is the diagnostic key. The aim was to evaluate the effect on outcome of adherence to European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), and Swedish guidelines regarding neuroimaging before LP., Methods: The cohort comprised 815 adult ABM patients in Sweden registered prospectively between 2008 and 2015. Primary endpoint was in-hospital mortality and secondary endpoint was favorable outcome at 2-6 months of follow-up., Results: Indications for neuroimaging before LP existed in 7%, 32%, and 65% according to Swedish, ESCMID, and IDSA guidelines, respectively. The adjusted odds ratio (aOR) was 0.48 (95% confidence interval [CI], .26-.89) for mortality and 1.52 (95% CI, 1.08-2.12) for favorable outcome if Swedish guidelines were followed. ESCMID guideline adherence resulted in aOR of 0.68 (95% CI, .38-1.23) for mortality and 1.05 (95% CI, .75-1.47) for favorable outcome. Following IDSA recommendations resulted in aOR of 1.09 (95% CI, .61-1.95) for mortality and 0.59 (95% CI, .42-.82) for favorable outcome. Performing prompt vs neuroimaging-preceded LP was associated with aOR of 0.38 (95% CI, .18-.77) for mortality and 2.11 (95% CI, 1.47-3.00) for favorable outcome. The beneficial effect of prompt LP was observed regardless of mental status and immunosuppression., Conclusions: Adherence to Swedish guidelines in ABM is associated with decreased mortality and increased favorable outcome in contrast to adherence to ESCMID or IDSA recommendations. Our findings support that impaired mental status and immunocompromised state should not be considered indications for neuroimaging before LP in patients with suspected ABM., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Adult bacterial meningitis (ABM) caused by non-Pseudomonas (Ps.) aeruginosa Pseudomonas (NPAP) species infection has rarely been reported. The clinical characteristics of 52 cases of Pseudomonas ABM (11 NPAP- and 41 Ps. aeruginosa-related meningitis) collected during a 30-year study period (1986-2015) were included. Eleven cases of NPAP ABM were identified in the literature, and their clinical data were also collected. Therefore, a total of 22 NPAP ABM cases were enrolled. The clinical characteristics of the NPAP ABM and Ps. aeruginosa ABM groups were compared. Of the implicated NPAP strains, Ps. putida and Ps. stutzeri were the most common (7 cases each), followed by Ps. mendocina in 4, Ps. fluorescens in 1, Ps. fulva in 1, Ps. alcaligenes in 1, and Ps. mosselii in 1. Of the 22 cases, 50% (11/22) had an underlying postneurosurgical state. Fever (77.3%, 17/22) and altered consciousness (45.5%, 10/22) were the most common clinical presentations. Antibiotic non-susceptibility was found in 3 strains of Ps. putida and 1 Ps. mosselii strain. Compared to the patients with Ps. aeruginosa ABM, those with NPAP ABM had a higher incidence of spontaneous infections and a better survival rate. In conclusion, although Ps. putida, Ps. stutzeri and Ps. mendocina were the major implicated strains of NPAP ABM, the clinical characteristics of this specific group of ABM demonstrated marked heterogeneity. Even though the cases with NPAP ABM had better therapeutic results than those with Ps. aeruginosa ABM, further large-scale studies are needed to better delineate this specific group of ABM., (Copyright © 2017. Published by Elsevier Taiwan.)

Aim: To determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and to show the impact of Gram-negative rods and the differences between patient characteristics and the clinical and prognostic measures in Gram-negative and Gram-positive meningitis., Material and Methods: In this prospective, single-center study, we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records., Results: Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and a median age of 50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%) were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram-positives (p=0.034). The duration between surgery and meningitis was shorter in Gram-negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal fluid protein and lactate levels were higher and glucose level was lower in cases of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049)., Conclusion: In NM, Gram-negative pathogens were seen more frequently; A. baumanni was the predominant pathogen; and NM caused by Gram-negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram-positives.

Background: The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities., Methods: Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients., Results: In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis., Conclusions: Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms that need to be fought. They should be rather seen as well orchestrated clean-up mechanisms, which may today be somewhat too active in a few very specific constellations, such as meningitis under antibiotic treatment and aSAH after surgical or endovascular exclusion of the aneurysm.

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and 52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%; 95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8-35.1), dyspnea (OR 4.2; 95%CI 1.5-12.0) and HIV infection (OR 3.3; 95%CI 1.1-10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.

Multiregional outbreaks of meningitis-like disease caused by Elizabethkingia miricola were confirmed in black-spotted frog farms in China in 2016. Whole-genome sequencing revealed that this amphibian E. miricola strain is closely related to human clinical isolates. Our findings indicate that E. miricola can be epizootic and may pose a threat to humans.

This is a retrospective study to evaluate epidemiology and etiologies of childhood meningitis in Kuwait after the routine introduction of the pneumococcal conjugate vaccine. The data was collected from 196 patients in the period of 2010-2014. Aseptic meningitis accounted for 51% of the cases, bacterial meningitis accounted for 29% cases and partially treated meningitis were 20%. Organisms causing bacterial meningitis were: Streptococcus pneumoniae 40.4%, Neisseria meningitidis 17.6%, Haemophilus spp. 12.2%, other gram positive or negative 19.3%, and Group B Streptococcus 8.8%. The hospitalization was complicated by admission to the ICU in 16.3% patients. Sequelae on discharge were seen in 4%, and 2.5% died of complications of meningitis. In children with pneumococcal meningitis, 48% were admitted to the ICU, 35% were discharged with sequelae and 13% died. In the era of post pneumococcal conjugate vaccination, S. pneumoniae remains the leading cause of bacterial meningitis with the greatest morbidity and mortality., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bacterial meningitis is a significant cause of morbidity and mortality in the developing world. However, limited research has focused on the diagnosis and management of meningitis in resource-limited settings., Methods: We designed a prospective case series of children admitted to a large, academic referral hospital with acute meningitis syndrome. Data were collected on age, time of presentation, prior antibiotics, cerebrospinal fluid (CSF) parameters, antibiotic and steroid prescription, and clinical outcome., Results: Data on 99 patients were collected and analyzed. Most of the patients were males, n=69 (70%), and were from a rural area, n=83 (84%). Incomplete vaccination was common, n=36 (36%) and many have evidence of malnutrition, n=25 (38%). Most patients, n=64 (72%), had received antibiotics prior to admission with a mean duration of symptoms of 4.9 days prior to admission. The CSF white blood cell (WBC) count was higher in those who had not received prior antibiotics though it was elevated in both groups. The CSF WBC count was not associated with survival; malnutrition and length of symptoms prior to admission were both associated with decreased survival., Conclusions: While use of antibiotics prior to obtaining CSF in patients with acute meningitis syndrome may decrease their CSF WBC count, it is not clinically significant. Many patients had a significant delay in presentation that had an effect on survival, This is a potentially modifiable risk factor despite the resourcelimited setting.

Background: Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program., Methods: Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time., Results: The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period., Conclusions: During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.