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Corticosteroids for acute bacterial meningitis

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Brouwer, Matthijs C, McIntyre, Peter, Prasad, Kameshwar, van de Beek, Diederik·2015·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd004405.pub5PMC PMC6491272
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Abstract

BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. SEARCH METHODS: We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. MAIN RESULTS: We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events. AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.

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  1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Chichester, UK: Wiley-Blackwell.
  2. van de Beek 2007 van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD004405.pub2] References: · DOI
  3. Timothy S. Leung, BScPharm ACPR PharmD Candidate Aaron M. Tejani, BScPharm PharmD I agree with the conflict of interest statement below: I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback. Reply Based on the chosen inclusion criteria we did not exclude studies from countries with high HIV positivity rates. To identify differences between areas of inclusion, which include HIV positivity but also e.g. malnourishment and access to health care, we performed the subgroup analysis by income status. We agree there is lack of detail in the adverse events reporting in the included studies and thereby selective reporting. However, we feel this does not merit a full update of the review.

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Authors
Brouwer, M. C., McIntyre, P., Prasad, K., & van de Beek, D.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • The University of Sydney (AU)
  • All India Institute of Medical Sciences (IN)
  • University of Amsterdam; Department of Neurology, Academic Medical Centre; P.O. Box 22660 Amsterdam Netherlands 1100 DE
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2015-09-12
Volume
2018
Issue
11
Pages
CD004405-CD004405
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd004405.pub5
PMC
PMC6491272
OpenAlex
W2105434315
Cited by
809
References
100
Citations by year
2026: 13 · 2025: 43 · 2024: 57 · 2023: 34 · 2022: 45 · 2021: 39 · 2020: 64 · 2019: 52 · 2018: 57 · 2017: 56 · 2016: 60 · 2015: 45 · 2014: 36 · 2013: 27 · 2012: 43
FWCI
8.82
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
Funders
  • ZonMw (#916.13.078, 016116358, #916.76.023)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (916.13.078, 916.76.023, 016.116.358)
  • FP7 Ideas: European Research Council (281156)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
  • Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
Keywords
corticosteroids, acute bacterial meningitis, mortality, hearing loss, neurological sequelae, children, adults, low-income countries, corticosteroid adverse effects, treatment timing, causative organisms, quality of evidence, subgroup analysis, risk of bias, low-value care, cost-effectiveness
MeSH terms
Acute Disease, Adolescent, Adult, Anti-Inflammatory Agents, Child, Developing Countries, Dexamethasone, Glucocorticoids, Humans, Hydrocortisone, Prednisolone, Randomized Controlled Trials as Topic, Meningitis, Bacterial, Developed Countries, Hearing Loss

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