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Background In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection.
Methods We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization.
Results A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27).
Conclusions Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499
[controlled-trials.com]
.)
Source Information
From the College of Medicine (M.S., S.B.G., C.J.M.W., N.F., Y.N., A.C., E.E.Z.) and the Malawi–Liverpool–Wellcome Programme of Clinical Tropical Research (S.B.G., N.F.) — both in Blantyre, Malawi; the Nuffield Department of Clinical Laboratory Science (M.S.) and the Nuffield Department of Medicine (T.E.A.P.) — both at the University of Oxford, Oxford, United Kingdom; the Liverpool School of Tropical Medicine, Liverpool, United Kingdom (M.S., S.B.G., N.F., D.G.L.); and the London School of Hygiene and Tropical Medicine, London (C.J.M.W.).
Address reprint requests to Dr. Scarborough at the Nuffield Department of Clinical Laboratory Science, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom, or at matthew.scarborough{at}ndcls.ox.ac.uk.
Related Letters:
Corticosteroids for Bacterial Meningitis
Chan E. D., Ong C. W., Hsu L. Y., Tambyah P. A., Taha M.-K., Alonso J.-M., Siberry G. K., McMillan J. A., Mai N. T. H., Thwaites G., Farrar J. J., Scarborough M., Gordon S., Peto T.
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N Engl J Med 2008;
358:1399-1401, Mar 27, 2008.
Correspondence
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