Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis

Abstract

In this nationwide prospective cohort study, we evaluated the implementation of adjunctive dexamethasone therapy in Dutch adults with pneumococcal meningitis. From March 2006 through January 2009, all Dutch patients over 16 years old with community-acquired pneumococcal meningitis were prospectively evaluated. Outcome was classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Clinical characteristics and outcome were compared with a similar nationwide cohort of 352 patients with pneumococcal meningitis from a previous period before guidelines recommended dexamethasone therapy (1998-2002). A multivariable prognostic model was used to adjust for differences in case mix between the 2 cohorts. We evaluated 357 episodes with pneumococcal meningitis in 2006-2009. Characteristics on admission were comparable with the earlier cohort (1998-2002). Dexamethasone was started with or before the first dose of antibiotics in 84% of episodes in 2006-2009 and 3% in 1998-2002. At discharge, unfavorable outcome was present in 39% in 2006-2009 and 50% in 1998-2002 (odds ratio [OR] 0.63; 95% confidence interval [CI] 0.46-0.86; p = 0.002). Rates of death (20% vs 30%; p = 0.001) and hearing loss (12% vs 22%; p = 0.001) were lower in 2006-2009. Differences in outcome remained after adjusting for differences in case mix between cohorts. Dexamethasone therapy has been implemented on a large scale as adjunctive treatment of adults with pneumococcal meningitis in the Netherlands. The prognosis of pneumococcal meningitis on a national level has substantially improved after the introduction of adjunctive dexamethasone therapy. This study provides Class III evidence that dexamethasone (10 mg IV, given every 6 hours for 4 days started before or with the first dose of parenteral antibiotics) reduced the proportion of patients with unfavorable outcomes (Glasgow Outcome Scale score of 1 to 4) in the 2006-2009 cohort, as compared to the 1998-2002 cohort (39% vs 50%; OR 0.63; 95% CI 0.46-0.86; p = 0.002). Mortality rate (20% vs 30%; absolute risk difference 10%; 95% CI 4%-17%; p = 0.001) was also lower in 2006-2009.