Meningitis - Adjunctive Steroids in Adults

12/04/2002

Question: What is the efficacy of adjunctive steroid therapy for bacterial meningitis, especially in adult patients?

 Link Directly to Fulltext article in Ovid

<1> Unique Identifier: 0

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.

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

 Link Directly to Fulltext Article at Publisher

<4>

Unique Identifier:10401941

Authors: Thomas R. Le Tulzo Y. Bouget J. Camus C. Michelet C. Le Corre P. Bellissant E.

Institution: Clinique des Maladies Infectieuses et Reanimation Medicale, Hopital Pontchaillou-CHU Rennes, France. remi.thomas@univ-rennes1.fr

Title: Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group.

Source: Intensive Care Medicine. 25(5):475-80, 1999 May.

Abstract: OBJECTIVE: To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults. DESIGN: Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30. RESULTS: Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion. CONCLUSION: Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae. CAS Registry/EC Number 0 (Glucocorticoids, Synthetic). 0 (Penicillins). 50-02-2 (Dexamethasone).