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In most developed settings, the use of adjunctive dexamethasone therapy in adults and children with bacterial meningitis is regarded as standard practice. However, little is known about the potential role of such therapy in developing countries or in areas with a high prevalence of HIV infection.
To address this gap, investigators conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) among 465 adults who were admitted to a hospital in Blantyre, Malawi, with bacterial meningitis. All study participants received ceftriaxone (2 mg twice daily) for 10 days. More than 80% of the study population was infected with HIV.
In an intent-to-treat analysis, 40-day mortality did not differ significantly between patients that received dexamethasone (56%) and those that received placebo (53%). This finding also held true in an analysis that was restricted to patients with proven pneumococcal meningitis. Rates of disability or death, and rates of adverse events, including hearing impairment, were also similar between the groups.
Scarborough M et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 2007 Dec 13; 357:2441.
Greenwood BM. Corticosteroids for acute bacterial meningitis. N Engl J Med 2007 Dec 13; 357:2507.
Comment
Despite the use of effective antibiotic therapy, mortality rates from bacterial meningitis remain unacceptably high in developing regions that also have a high prevalence of HIV infection. In this study, more than 50% of the patients died within 40 days of enrollment, regardless of whether they received adjunctive dexamethasone therapy. In contrast, in a similar trial in Vietnam, where <1% of the study population was infected with HIV, the overall mortality rate was much lower (11%), and adjunctive dexamethasone therapy was beneficial, although only in patients with microbiologically proven disease (N Engl J Med 2007; 357:24).
Overall, the literature supports the theory that the use of steroids in developing countries with a high prevalence of HIV infection has no value, probably as a result of a more pathogenic strain of organisms, mixed infections that may worsen with steroid use, or underlying HIV-associated immune compromise, resulting in poor response to treatment. An editorialist rightly suggests that we shift our focus to preventing infections through the use of conjugate vaccines.