Articles
Community-acquired bacterial meningitis in adults in the Netherlands, 2006–14: a prospective cohort study

https://doi.org/10.1016/S1473-3099(15)00430-2Get rights and content

Summary

Background

We studied causative pathogens, clinical characteristics, and outcome of adult community-acquired bacterial meningitis after the introduction of adjunctive dexamethasone treatment and nationwide implementation of paediatric conjugate vaccines.

Methods

In this cohort study, we prospectively assessed adults (age >16 years) with community-acquired bacterial meningitis in the Netherlands, identified through the National Reference Laboratory for Bacterial Meningitis or individual physicians between Jan 1, 2006, and July 1, 2014. We identified independent predictors of an unfavourable outcome (Glasgow Outcome Scale score 1–4) by logistic regression.

Findings

We assessed 1412 episodes of community-acquired bacterial meningitis. Incidence declined from 1·72 cases per 100 000 adults per year in 2007–08, to 0·94 per 100 000 per year in 2013–14. Streptococcus pneumoniae caused 1017 (72%) of 1412 episodes. Rates of adult bacterial meningitis decreased most sharply among pneumococcal serotypes included in paediatric conjugate vaccine, and in meningococcal meningitis. We found no evidence of serotype or serogroup replacement. The overall case fatality rate was 244 (17%) of 1412 episodes and unfavourable outcome occurred in 531 (38%) of 1412 episodes. Predictors of unfavourable outcome were advanced age, absence of otitis or sinusitis, alcoholism, tachycardia, lower score on the Glasgow Coma Scale, cranial nerve palsy, a cerebrospinal fluid white-cell count lower than 1000 cells per μL, a positive blood culture, and a high serum C-reactive protein concentration. Adjunctive dexamethasone was administered for 1234 (89%) of 1384 assessed episodes. The multivariable adjusted odds ratio of dexamethasone treatment for unfavourable outcome was 0·54 (95% CI 0·39–0·73).

Interpretation

The incidence of adult bacterial meningitis has decreased substantially, which is partly explained by herd protection by paediatric conjugate vaccines. Adjunctive dexamethasone treatment was associated with substantially improved outcome.

Funding

European Research Council, National Institute of Public Health and the Environment, European Union, Academic Medical Center, and Netherlands Organization for Health Research and Development.

Introduction

Bacterial meningitis is associated with substantial mortality and morbidity.1 The epidemiology and treatment of bacterial meningitis has changed over the past 15 years.2, 3 The routine use of protein–polysaccharide conjugate vaccines in childhood against common causative pathogens of bacterial meningitis has reduced the overall incidence, affecting the distributions of causative pathogens and the age groups most often affected.2, 4 The introduction of new treatments, such as dexamethasone as adjunctive treatment, might have affected national outcomes of bacterial meningitis.5, 6 In 2006, we started a prospective cohort study to identify and characterise host genetic traits and bacterial genetic factors controlling occurrence and outcome of bacterial meningitis (MeninGene).7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Here, we report data from this study, including the incidence, causative pathogens, clinical features, and prognostic factors in adults with community-acquired bacterial meningitis in the Netherlands from 2006 to 2014.

Section snippets

Study population

We identified adults (patients older than age 16 years) who had bacterial meningitis in the Netherlands between Jan 1, 2006, and July 1, 2014, and who were listed in the database of the Netherlands Reference Laboratory for Bacterial Meningitis. This laboratory receives cerebrospinal fluid and blood samples from roughly 85% of all patients with bacterial meningitis in the Netherlands (population 16·9 million).20, 21 The laboratory provided daily updates of the names of hospitals where patients

Results

1887 episodes of bacterial meningitis were identified, 1736 (92%) by the reference laboratory and 151 (8%) by physicians (figure 1). 240 (13%) of 1887 episodes were excluded from the cohort and 235 (12%) met exclusion criteria, resulting in 1412 (75%) episodes in 1391 patients (figure 1).

Median age was 61 years (table 1). A history of splenectomy or cerebrospinal fluid leak was present in 71 (5%) of 1374 episodes. For 457 (33%) of 1380 episodes, the patient had used immunosuppressive drugs or

Discussion

Our findings show that the incidence of adult bacterial meningitis has decreased since the introduction of conjugate vaccines, primarily because of falls in pneumococcal and meningococcal meningitis. Incidence decreased most sharply among pneumococcal serotypes included in the seven-valent and ten-valent conjugate vaccines; these vaccines were introduced in the Netherlands in 2006 and 2011. A surveillance study4 of 17·4 million people in the USA during 1998–2007, showed a similar effect of herd

References (42)

  • D van de Beek et al.

    Clinical features and prognostic factors in adults with bacterial meningitis

    N Engl J Med

    (2004)
  • MC Thigpen et al.

    Bacterial meningitis in the United States, 1998–2007

    N Engl J Med

    (2011)
  • J de Gans et al.

    Dexamethasone in adults with bacterial meningitis

    N Engl J Med

    (2002)
  • D van de Beek et al.

    Dexamethasone in adults with community-acquired bacterial meningitis

    Drugs

    (2006)
  • MC Brouwer et al.

    Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis

    Neurology

    (2010)
  • MJ Lucas et al.

    Delayed cerebral thrombosis in bacterial meningitis: a prospective cohort study

    Intensive Care Med

    (2013)
  • MJ Lucas et al.

    Outcome in patients with bacterial meningitis presenting with a minimal Glasgow Coma Scale score

    Neurol Neuroimmunol Neuroinflamm

    (2014)
  • MJ Lucas et al.

    Endocarditis in adults with bacterial meningitis

    Circulation

    (2013)
  • B Woehrl et al.

    Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

    J Clin Invest

    (2011)
  • MC Brouwer et al.

    Plasminogen activator inhibitor-1 influences cerebrovascular complications and death in pneumococcal meningitis

    Acta Neuropathol

    (2014)
  • JR Piet et al.

    Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis

    J Infect Dis

    (2014)
  • Cited by (266)

    View all citing articles on Scopus

    Contributed equally

    View full text