Trial of dexamethasone treatment for severe bacterial meningitis in adults

Objective: To evaluate the clinical benefit of early adjunctive dexamethaso ne 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 initiat ion 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 patie nts cured without any neurologic sequelae on day 30. Results: Sixty patients were enrolled, predominantly with a severe form sin ce 85 % required ICU stay and 43 % mechanical ventilation. Streptococcus pn eumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. Th e study had to be stopped prematurely because of a new national recommendat ion of experts to use third generation cephalosporin and vancomycin as a re sult of the increasing rate of penicillin-resistant S. pneumoniae in France . After the third sequential analysis by the triangular statistical test, t he 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 dexamet hasone as an adjunctive therapy for bacterial meningitis in adults. Moreove r this treatment impairs antibiotic penetration into the cerebrospinal flui d (CSF) that can lead to therapeutic failure, particularly in areas with hi gh or increasing rates of penicillin-resistant S. pneumoniae.