Dexamethasone in adults with bacterial meningitis

N Engl J Med. 2002 Nov 14;347(20):1549-56. doi: 10.1056/NEJMoa021334.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Chemotherapy, Adjuvant
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use*
  • Double-Blind Method
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Male
  • Meningitis, Bacterial / complications
  • Meningitis, Bacterial / drug therapy*
  • Meningitis, Bacterial / mortality
  • Meningitis, Meningococcal / complications
  • Meningitis, Meningococcal / drug therapy
  • Meningitis, Pneumococcal / complications
  • Meningitis, Pneumococcal / drug therapy
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Glucocorticoids
  • Dexamethasone