Background Mortality and morbidity rates are high among adultswith acute bacterial meningitis, especially those with pneumococcalmeningitis. In studies of bacterial meningitis in animals, adjuvanttreatment 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 minutesbefore or with the first dose of antibiotic and was given every6 hours for four days. The primary outcome measure was the scoreon the Glasgow Outcome Scale at eight weeks (a score of 5, indicatinga favorable outcome, vs. a score of 1 to 4, indicating an unfavorableoutcome). A subgroup analysis according to the causative organismwas performed. Analyses were performed on an intention-to-treatbasis.
Results A total of 301 patients were randomly assigned to atreatment group: 157 to the dexamethasone group and 144 to theplacebo group. The base-line characteristics of the two groupswere similar. Treatment with dexamethasone was associated witha reduction in the risk of an unfavorable outcome (relativerisk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03).Treatment with dexamethasone was also associated with a reductionin mortality (relative risk of death, 0.48; 95 percent confidenceinterval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcalmeningitis, there were unfavorable outcomes in 26 percent ofthe dexamethasone group, as compared with 52 percent of theplacebo group (relative risk, 0.50; 95 percent confidence interval,0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred intwo patients in the dexamethasone group and in five patientsin the placebo group.
Conclusions Early treatment with dexamethasone improves theoutcome in adults with acute bacterial meningitis and does notincrease the risk of gastrointestinal bleeding.
Source Information
From the Department of Neurology, Academic Medical Center, Amsterdam.
Address reprint requests to Dr. de Gans at the Academic Medical Center, University of Amsterdam, Department of Neurology H2, P.O. Box 22660, 1100 DD Amsterdam, the Netherlands, or at j.degans{at}amc.uva.nl.
Dexamethasone in Adults with Bacterial Meningitis
Tabas J. A., Chambers H. F., Tancredi D. N., Binder W. D., Abril V., Ortega E., Joffe A. R., Poshkus M., Obaro S., de Gans J., van de Beek D., Tunkel A. R., Scheld W. M.
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N Engl J Med 2003;
348:954-957, Mar 6, 2003.
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