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Review
, 2015 (9), CD004405

Corticosteroids for Acute Bacterial Meningitis

Affiliations
Review

Corticosteroids for Acute Bacterial Meningitis

Matthijs C Brouwer et al. Cochrane Database Syst Rev.

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.

Conflict of interest statement

Matthijs C Brouwer: none known. Peter McIntyre: none known. Kameshwar Prasad: none known. Diederik van de Beek is a primary author of one of the included trials (de Gans 2002). Matthijs C Brouwer independently extracted data and assessed quality.

Figures

Figure 1
Figure 1
'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study.
Figure 2
Figure 2
'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figure 3
Figure 3
Forest plot of comparison: 1 All patients, outcome: 1.1 Mortality.
Figure 4
Figure 4
Forest plot of comparison: 1 All patients, outcome: 1.2 Severe hearing loss.
Figure 5
Figure 5
Forest plot of comparison: 1 All patients, outcome: 1.3 Any hearing loss.
Figure 6
Figure 6
Forest plot of comparison: 1 All patients, outcome: 1.6 Adverse events.
Analysis 1.1
Analysis 1.1
Comparison 1 All patients, Outcome 1 Mortality.
Analysis 1.2
Analysis 1.2
Comparison 1 All patients, Outcome 2 Severe hearing loss.
Analysis 1.3
Analysis 1.3
Comparison 1 All patients, Outcome 3 Any hearing loss.
Analysis 1.4
Analysis 1.4
Comparison 1 All patients, Outcome 4 Short‐term neurological sequelae.
Analysis 1.5
Analysis 1.5
Comparison 1 All patients, Outcome 5 Long‐term neurological sequelae.
Analysis 1.6
Analysis 1.6
Comparison 1 All patients, Outcome 6 Adverse events.
Analysis 2.1
Analysis 2.1
Comparison 2 Children, Outcome 1 Mortality.
Analysis 2.2
Analysis 2.2
Comparison 2 Children, Outcome 2 Severe hearing loss.
Analysis 2.3
Analysis 2.3
Comparison 2 Children, Outcome 3 Any hearing loss.
Analysis 3.1
Analysis 3.1
Comparison 3 Adults, Outcome 1 Mortality.
Analysis 3.2
Analysis 3.2
Comparison 3 Adults, Outcome 2 Any hearing loss.
Analysis 3.3
Analysis 3.3
Comparison 3 Adults, Outcome 3 Short‐term neurological sequelae.
Analysis 4.1
Analysis 4.1
Comparison 4 Causative species, Outcome 1 Mortality.
Analysis 4.2
Analysis 4.2
Comparison 4 Causative species, Outcome 2 Severe hearing loss in children ‐ non‐Haemophilus influenzae species.
Analysis 4.3
Analysis 4.3
Comparison 4 Causative species, Outcome 3 Severe hearing loss in children ‐ Haemophilus influenzae.
Analysis 5.1
Analysis 5.1
Comparison 5 Income of countries, Outcome 1 Mortality ‐ all patients.
Analysis 5.2
Analysis 5.2
Comparison 5 Income of countries, Outcome 2 Severe hearing loss ‐ all patients.
Analysis 5.3
Analysis 5.3
Comparison 5 Income of countries, Outcome 3 Any hearing loss.
Analysis 5.4
Analysis 5.4
Comparison 5 Income of countries, Outcome 4 Short‐term neurological sequelae ‐ all patients.
Analysis 5.5
Analysis 5.5
Comparison 5 Income of countries, Outcome 5 Mortality ‐ children.
Analysis 5.6
Analysis 5.6
Comparison 5 Income of countries, Outcome 6 Severe hearing loss ‐ children.
Analysis 5.7
Analysis 5.7
Comparison 5 Income of countries, Outcome 7 Short‐term neurological sequelae ‐ children.
Analysis 5.8
Analysis 5.8
Comparison 5 Income of countries, Outcome 8 Severe hearing loss in children due to non‐Haemophilus influenzae species.
Analysis 5.9
Analysis 5.9
Comparison 5 Income of countries, Outcome 9 Mortality ‐ adults.
Analysis 5.10
Analysis 5.10
Comparison 5 Income of countries, Outcome 10 Any hearing loss adults.
Analysis 6.1
Analysis 6.1
Comparison 6 Timing of steroids, Outcome 1 Mortality.
Analysis 6.2
Analysis 6.2
Comparison 6 Timing of steroids, Outcome 2 Severe hearing loss.
Analysis 6.3
Analysis 6.3
Comparison 6 Timing of steroids, Outcome 3 Any hearing loss.
Analysis 6.4
Analysis 6.4
Comparison 6 Timing of steroids, Outcome 4 Short‐term neurologic sequelae.
Analysis 7.1
Analysis 7.1
Comparison 7 Study quality, Outcome 1 Mortality.
Analysis 7.2
Analysis 7.2
Comparison 7 Study quality, Outcome 2 Severe hearing loss.
Analysis 7.3
Analysis 7.3
Comparison 7 Study quality, Outcome 3 Any hearing loss.
Analysis 7.4
Analysis 7.4
Comparison 7 Study quality, Outcome 4 Short‐term neurological sequelae.
Analysis 8.1
Analysis 8.1
Comparison 8 Sensitivity analysis ‐ worst‐case scenario, Outcome 1 Severe hearing loss.
Analysis 8.2
Analysis 8.2
Comparison 8 Sensitivity analysis ‐ worst‐case scenario, Outcome 2 Any hearing loss.
Analysis 8.3
Analysis 8.3
Comparison 8 Sensitivity analysis ‐ worst‐case scenario, Outcome 3 Short‐term neurological sequelae.
Analysis 8.4
Analysis 8.4
Comparison 8 Sensitivity analysis ‐ worst‐case scenario, Outcome 4 Long‐term neurological sequelae.

Update of

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