Abstract & Commentary
Source: de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-1556.
The role of corticosteroids in minimizing sequelae of acute bacterial meningitis has been debated strongly. The authors of this multinational European study sought to determine whether administration of steroids improved neurologic outcome in adults with suspected meningitis. Patients were eligible if they had undergone a lumbar puncture revealing cerebrospinal fluid (CSF) that was cloudy, showed bacteria, or had a leukocyte count greater than 1000/mm3. Subjects were randomized to receive either placebo or dexamethasone 10 mg, administered 15-20 minutes prior to antibiotics and then every six hours for four days. All patients were treated empirically with amoxicillin, which is appropriate monotherapy in the Netherlands. The primary outcome was the Glasgow Outcome Scale score at eight weeks, in which a score of five was favorable and lower scores unfavorable.
In the study, 301 patients were randomized. Baseline characteristics were similar between treatment and placebo groups. Pneumococcus was isolated in 35% of patients, Neisseria meningitidis in 32%, and other bacteria in 10%; negative cultures were noted in 22%. The number of patients with unfavorable outcomes at eight weeks was significantly smaller in the dexamethasone group (15% vs. 25%, relative risk 0.59 [95% CI 0.37—0.94]). Mortality also was lower in the steroid-treated group (7% vs. 15%, relative risk 0.48 [95% CI 0.24 —0.96]). A planned subgroup analysis showed that outcome and mortality improvements only were detectable among patients with pneumococcal meningitis. Treatment with dexamethasone did not result in an increased risk of gastrointestinal bleeding or other adverse events. The authors conclude that dexamethasone administered prior to antibiotic therapy improves the outcomes of adults with acute bacterial meningitis without increasing the risk of complications.
Commentary by David J. Karras, MD, FAAEM, FACEP
Strong evidence favoring the benefit of corticosteroids in the treatment of acute bacterial meningitis began emerging a decade ago. An early and highly influential study published in 1989 showed that dexamethasone, when administered just prior to antibiotics, greatly reduce the risk of neurological sequelae in an era when manyu infections were due to Haemophilus influenzae type B (HIB). 1 This led to recommendations that steroids be used empirically in children with acute meningitis. The data from studies of adults have been less compelling and opinions on the role of steroids for this group have been divided.
The microbiology of meningitis has changed in the last 10 years, with HIB infections now uncommon in children and accounting for a small number of infections in adult patients. Multiple studies showed steroids to be of marginal benefit in pneumococcal infections, now the most common cause of meningitis in all age groups except neonates. An expert review in the New England Journal of Medicine concluded that steroids should be limited to children not vaccinated against HIB and to adults with high CSF bacterial counts and increased intracranial pressure.2 In patients not meeting these criteria, the risk of serious gastrointestinal bleeding was felt to be greater than the marginal benefit of steroids.
The present article is far stronger than most studies of dexamethasone in meningitis, most of which have very small sample sizes. In light of how equivocal the prior data have been, I would be inclined to use this study as my rationale for routinely administering steroids to adults with acute bacterial meningitis.
Dr. Karras, Associate Professor of Emergency Medicine, Department of Emergency Medicine Temple University School of Medicine, Director of Emergency Medicine Research, Temple University Hospital, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.
1. Girfis NI, et al. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 1989;8:848-851.
2. Quagliarello VJ. Treatment of bacterial meningitis. N Engl J Med 1997;336:708-716.