Corticosteroids for acute bacterial meningitis

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004405.

van de Beek D, de Gans J, McIntyre P, Prasad K.

Academic Medical Center University of Amsterdam, Department of Neurology, Center for Infection and Immunity Amsterdam (CINIMA), P.O. Box 22700, 1100 DE, Amsterdam, Netherlands.

BACKGROUND: In experimental studies, the clinical outcome of acute bacterial meningitis has been related to the severity of the inflammatory process in the subarachnoidal space. Treatment with corticosteroids can reduce this inflammatory response and thereby may improve outcome. We conducted a meta-analysis of randomised controlled trials (RCTs) of adjuvant corticosteroids in the treatment of acute bacterial meningitis. 

OBJECTIVES: We conducted a systematic review examining the efficacy and safety of adjuvant corticosteroid therapy in acute bacterial meningitis. 

SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006); MEDLINE (1966 to July 2006); EMBASE (1974 to June 2006); Current Contents (2001 to June 2006); and reference lists of all articles. We also contacted manufacturers and researchers in the field. 

SELECTION CRITERIA: Eligible published and non-published RCTs on corticosteroids as adjuvant therapy in acute bacterial meningitis. Patients of any age and in any clinical condition, treated with antibacterial agents and randomised to corticosteroid therapy (or placebo) of any type, could be included. At least case fatality rate or hearing loss had to be recorded for inclusion. 

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Adverse effects were collected from the trials. Additional analyses were performed for children and adults, causative organisms, and low-income and developed countries. 

MAIN RESULTS: Eighteen studies involving 2750 people were included. Overall, adjuvant corticosteroids were associated with lower case fatality (relative risk (RR) 0.83, 95% CI 0.71 to 0.99), lower rates of severe hearing loss (RR 0.65, 95% CI 0.47 to 0.91) and long-term neurological sequelae (RR 0.67, 95% CI 0.45 to 1.00). In children, corticosteroids reduced severe hearing loss (RR 0.61, 95% CI 0.44 to 0.86). In adults, corticosteroids gave significant protection against death (RR 0.57, 95% CI 0.40 to 0.81) and short-term neurological sequelae (RR 0.42, 95% CI 0.22 to 0.87). Subgroup analysis for causative organisms showed that corticosteroids reduced mortality in patients with meningitis due to Streptococcus pneumoniae (RR 0.59, 95% CI 0.45 to 0.77) and reduced severe hearing loss in children with meningitis due to Haemophilus influenzae (RR 0.37, 95% CI 0.20 to 0.68); subgroup analysis for patients with meningococcal showed a nonsignificant favourable trend in mortality (RR 0.71, 95% CI 0.31 to 1.62). Sub analyses for high-income and low-income countries of the effect of corticosteroids on mortality showed RRs of 0.83 (95% CI 0.52 to 1.05) and 0.87 (95% CI 0.72 to 1.05), respectively. Corticosteroids were protective against short-term neurological sequelae in patients with bacterial meningitis high-income countries (RR 0.56, 95% CI 0.3 to 0.84); in low-income countries this RR was 1.09 (95% CI 0.83 to 1.45). For children with bacterial meningitis admitted in high-income countries, corticosteroids showed a protective effect of on severe hearing loss (RR 0.61, 95% CI 0.41 to 0.90) and favourable point estimates for severe hearing loss associated with non-Haemophilus influenzae meningitis (RR 0.51, 95% CI 0.23 to 1.13) and short-term neurological sequelae (RR 0.72, 95% CI 0.39 to 1.33). For children in low-income countries, the use of corticosteroids was neither associated with benefit nor with harmful effects. Overall, adverse events were not increased significantly with the use of corticosteroids. 

AUTHORS’ CONCLUSIONS: Overall, corticosteroids significantly reduced rates of mortality, severe hearing loss and neurological sequelae. In adults with community-acquired bacterial meningitis, corticosteroid therapy should be administered in conjunction with the first antibiotic dose. In children, data support the use of adjunctive corticosteroids in children in high-income countries. We found no beneficial effect of corticosteroids for children in low-income countries.

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