Effect of the COVID-19 pandemic on clinical characteristics and outcomes of adult pneumococcal meningitis patients - a Dutch prospective nationwide cohort study.

PURPOSE: To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. METHODS: In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. RESULTS: We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8). CONCLUSION: During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.

Prospective multicenter evaluation of adherence to the Dutch guideline for children aged 0-16 years with fever without a source-febrile illness in children (FINCH) study.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. CONCLUSIONS: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment. WHAT IS KNOWN: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice. WHAT IS NEW: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections.

Global Case Fatality of Bacterial Meningitis During an 80-Year Period: A Systematic Review and Meta-Analysis.

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.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy.

OBJECTIVES: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. METHODS: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1ß, CRP and procalcitonin concentrations were measured with Luminex technology. RESULTS: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1ß (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). CONCLUSION: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Diagnostic prediction models for bacterial meningitis in children with a suspected central nervous system infection: a systematic review and prospective validation study.

OBJECTIVES: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation. METHODS: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM. RESULTS: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates. CONCLUSIONS: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing.

Genetic markers associated with host status and clonal expansion of Group B Streptococcus in the Netherlands.

Objectives: Certain Group B Streptococcus (GBS) genotypes are associated with invasive disease in neonates. We conducted a comparative genomic analysis of GBS isolates from neonatal disease and maternal carriage in the Netherlands to determine distribution of genetic markers between the two host groups. Methods: Whole genome sequencing was used to characterise 685 neonatal invasive isolates (2006-2021) and 733 maternal carriage isolates (2017-2021) collected in the Netherlands. Results: Clonal complex (CC) 17 and serotype III were significantly more common in disease while carriage isolates were associated with serotypes II, IV, V as well as CC1. Previously reported CC17-A1 sub-lineage was dominant among disease isolates and significantly less common in carriage. The phiStag1 phage, previously associated with expansion of invasive CC17 isolates in the Netherlands, was more common among disease isolates compared to carriage isolates overall, however it was equally distributed between CC17 isolates from carriage and disease. Prevalence of antimicrobial resistance genes was overall lower in disease compared to carriage isolates, but increased significantly over time, mediated by rise in prevalence of a multidrug resistance element ICESag37 among disease isolates. Conclusion: There is a stable association between certain GBS genotypes and invasive disease, which suggests opportunities for developing more precise disease prevention strategies based on GBS targeted screening. In contrast, GBS mobile genetic elements appear less likely to be correlated with carriage or disease, and instead are associated with clonal expansion events across the GBS population.

Recurrent bacterial meningitis in children in the Netherlands: a nationwide surveillance study.

OBJECTIVES: This study aimed to estimate the recurrence rate of culture-positive bacterial meningitis in children in the Netherlands. DESIGN: Nationwide surveillance study, using the database of the Netherlands Reference Laboratory for Bacterial Meningitis to identify patients with culture-positive bacterial meningitis during childhood. SETTING: The study was based in the Netherlands. PARTICIPANTS: A total of 9731 children with a first bacterial meningitis episode between 1 July 1987 and 30 June 2019 were identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Recurrence was defined as a subsequent episode >28 days, or caused by a different pathogen. Annual incidence and incidence rate ratios (IRRs) comparing the periods 1988-2003 and 2004-2019 were calculated. Predictors of recurrent meningitis were assessed using Cox proportional hazards regression. RESULTS: Sixty-three (0.6%) of the 9731 children with a first bacterial meningitis episode contracted recurrent meningitis. Neisseria meningitidis was the leading pathogen for first meningitis episodes (52%) and Streptococcus pneumoniae for recurrent episodes (52%). The median annual incidence of first episodes per 100 000 children decreased from 11.81 (IQR 11.26-17.60) in 1988-2003 to 2.60 (IQR 2.37-4.07) in 2004-2019 (IRR 0.25, 95% CI 0.23 to 0.26). The incidence of recurrences did not change: 0.06 (IQR 0.02-0.11) in 1988-2003 to 0.03 (IQR 0.00-0.06) in 2004-2019 (IRR 0.65, 95% CI 0.39 to 1.1). Age above 5 years (OR 3.6 (95% CI 1.5 to 8.3)) and a first episode due to Escherichia coli (OR 25.7 (95% CI 7.2 to 92.0)) were associated with higher risks of recurrence. CONCLUSION: The recurrence rate of childhood bacterial meningitis in the Netherlands was 0.6%. While the incidence rate of first episodes decreased substantially, this was not the case for recurrent episodes. Older age and a first episode due to E. coli were associated with higher recurrence risks.