Corticosteroids for acute bacterial meningitis

Matthijs C Brouwer, Peter McIntyre, Kameshwar Prasad, Diederik van de Beek, Matthijs C Brouwer, Peter McIntyre, Kameshwar Prasad, Diederik van de Beek

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

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

Source: PubMed

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