Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis

Abstract

Background: In this nationwide prospective cohort study, we evaluated the implementation of adjunctive dexamethasone therapy in Dutch adults with pneumococcal meningitis.

Methods: 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.

Results: 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.

Conclusions: 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.

Classification of evidence: 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.