Volume 6, Number 10;  July 19, 2006

Patient:

Session Handout:

Readings:

 Link Directly to Fulltext Article at Science Direct

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Unique Identifier [PMID]: 14998499

Authors: van de Beek D. de Gans J. McIntyre P. Prasad K.

Institution: Department of Neurology, Academic Medical Centre, University of Amsterdam, Netherlands. D.vandeBeek@amc.uva.nl

Title: Steroids in adults with acute bacterial meningitis: a systematic review. [Review] [32 refs]

Source: The Lancet Infectious Diseases. 4(3):139-43, 2004 Mar.

Abstract: Bacterial meningitis is uncommon but causes significant mortality and morbidity, despite optimum antibiotic therapy. A clinical trial in 301 patients showed a beneficial effect of adjunctive steroid treatment in adults with acute community-acquired pneumococcal meningitis, but data on other organisms or adverse events are sparse. This led us to do a quantitative systematic review of adjunctive steroid therapy in adults with acute bacterial meningitis. Five trials involving 623 patients were included (pneumococcal meningitis=234, meningococcal meningitis=232, others=127, unknown=30). Overall, treatment with steroids was associated with a significant reduction in mortality (relative risk 0.6, 95% CI 0.4-0.8, p=0.002) and in neurological sequelae (0.6, 0.4-1, p=0.05), and with a reduction of case-fatality in pneumococcal meningitis of 21% (0.5, 0.3-0.8, p=0.001). In meningococcal meningitis, mortality (0.9, 0.3-2.1) and neurological sequelae (0.5, 0.1-1.7) were both reduced, but not significantly. Adverse events, recorded in 391 cases, were equally divided between the treatment and placebo groups (1, 0.5-2), with gastrointestinal bleeding in 1% of steroid-treated and 4% of other patients. Since treatment with steroids reduces both mortality and neurological sequelae in adults with bacterial meningitis, without detectable adverse effects, routine steroid therapy with the first dose of antibiotics is justified in most adult patients in whom acute community-acquired bacterial meningitis is suspected. [References: 32]

Publication Type: Journal Article. Review.

Unique Identifier [PMID]: 12918010

Authors: van de Beek D. de Gans J. McIntyre P. Prasad K.

Title: Corticosteroids in acute bacterial meningitis.[see comment]. [Review] [63 refs]

Source: Cochrane Database of Systematic Reviews. (3):CD004405, 2003.

Abstract: BACKGROUND: Acute bacterial meningitis remains a disease with high mortality rate, ranging from 10 to 30 percent, despite advances in critical care. It has been estimated that between 5 to 40 percent of all patients can suffer hearing loss. The use of corticosteroids as adjuvant therapy in the treatment of acute bacterial meningitis is controversial despite several controlled clinical trials and three meta-analyses. In particular there are few data on the use of corticosteroids in adult meningitis. OBJECTIVES: We conducted a systematic review examining the efficacy and safety of adjuvant corticosteroid therapy in children and adults with acute bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 1, 2003)); MEDLINE (1966 to April 2002); EMBASE (1974 to April 2002); and HEALTHLINE (1988 to April 2002) and Current Contents for trials published before the April 1st 2002, and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Eligible studies were published or non-published randomised controlled trials 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 reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Eighteen studies involving 1853 people were included. Overall, adjuvant corticosteroids were associated with lower case fatality (relative risk (RR) 0.76, 95% confidence intervals (CI) 0.59 to 0.98) and lower rates of both severe hearing loss (RR 0.36, 95% CI 0.22 to 0.60) and long-term neurological sequelae (RR 0.66, 95% CI 0.44 to 0.99). In children, corticosteroids reduced severe hearing loss in bacterial meningitis caused by Haemophilus influenzae (RR 0.31, 95% CI 0.15 to 0.62), as well as in meningitis caused by other bacteria than H. influenzae (RR 0.42, 95%CI 0.20 to 0.89). In adults there was a reduction in case-fatality (RR 0.38, 95% CI 0.18 to 0.78), however there were few data. Adverse events were not increased significantly with the use of corticosteroids. REVIEWER'S CONCLUSIONS: Adjuvant corticosteroids are beneficial in the treatment of children with acute bacterial meningitis. The limited data available in adults shows a trend in favour of adjuvant corticosteroids but a definite recommendation must await more studies. ERRATUM: During the review process of this systematic review the results of the European Dexamethasone in Adulthood Bacterial Meningitis Trial were published. (De Gans 2002) In this prospective, randomised, double-blind, multicenter trial, which included 301 adults with bacterial meningitis, treatment with dexamethasone was associated with a reduction in mortality (relative risk of death, 0.48; 95 CI 0.24 to 0.96; p = 0.04). Therefore, dexamethasone should be given to all adults with bacterial meningitis and should be initiated before or with the first dose of antibiotics. [References: 63]

Publication Type: Journal Article. Meta-Analysis. Review.

 Link Directly to Fulltext Article at Publisher

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Unique Identifier [PMID]: 12432041

Authors: de Gans J. van de Beek D. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators.

Institution: Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands. j.degans@amc.uva.nl

Title: Dexamethasone in adults with bacterial meningitis.[see comment].

Source: New England Journal of Medicine. 347(20):1549-56, 2002 Nov 14.

Abstract: BACKGROUND: Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects. METHODS: We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group. CONCLUSIONS: Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding. Copyright 2002 Massachusetts Medical Society

Publication Type: Clinical Trial. Journal Article. Multicenter Study. Randomized Controlled Trial.

Resident Report / Department of Medicine & Grady Branch Library

Emory University School of Medicine

2006 Edition

Participating Faculty:  Carlos Del Rio MD  / Joyce Doyle MD / Lorenzo Difrancesco MD / Joel Mermis MD / Maunank Shah MD

Contact: Karl Woodworth