Trial of dexamethasone treatment for severe bacterial meningitis in adults

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.