Corticosteroids for acute bacterial meningitis.

Death and long-term disabilities are common outcomes of acute bacterial meningitis, especially in developing countries, even when highly effective antibiotic therapy is given. Therefore, improvement in the outcomes of acute bacterial meningitis is unlikely to come from developments in chemotherapy but rather from measures that alleviate the damage done before the causative bacteria are killed. Some of this damage is caused by bacterial toxins, but experiments in animals suggest that host inflammatory responses induced by bacterial products are also involved.1 Thus, there are strong theoretical grounds for believing that antiinflammatory drugs should improve the outcomes of acute bacterial meningitis. Establishing whether this is the case has taken more than 25 years,2 and the situation is still not entirely clear. Many of the early trials of corticosteroid therapy in acute bacterial meningitis were underpowered and had flaws in their designs. However, there is now a consensus, based largely on the results of meta-analyses rather than on individual, definitive trials, that in industrialized countries, the administration of dexamethasone to children with acute Haemophilus influenzae type b meningitis before the start of antibiotic therapy reduces the incidence of sequelae, especially deafness.3 The increasing use of the H. inf luenzae type b conjugate vaccines is reducing the burden of disease caused by this pathogen. The effect of dexamethasone on meningitis caused by other bacteria is less certain. Nevertheless, the administration of dexamethasone is now widely accepted as standard practice in the management of acute bacterial meningitis in children in the industrialized world. There is evidence, based largely on the results of a large multicenter trial in Europe, that dexamethasone also improves outcomes in adults in industrialized countries.4,5 Can these findings be translated to the developing world, where acute bacterial meningitis is many times more prevalent than it is in wealthy countries? The results of some early studies of corticosteroid therapy for the management of acute bacterial meningitis in children in less developed countries were encouraging.6-8 However, a trial involving 598 Malawian children, about one third of whom were positive for the human immunodeficiency virus (HIV), provided convincing evidence of a lack of any benefit.9 The negative outcome of this large, well-conducted trial has persuaded most pediatricians practicing in Africa that the routine administration of corticosteroids to children with acute bacterial meningitis is not indicated. Results from another Malawian trial suggest that, in this part of Africa, the same may be true for adults. In this issue of the Journal, Scarborough et al.10 report the results of a trial of dexamethasone in 465 Malawian patients 16 years of age or older with acute bacterial meningitis. Dexamethasone was given at a dose of 16 mg twice daily for 4 days in conjunction with ceftriaxone (given intravenously or intramuscularly in a nested, factorial trial). Overall mortality at 40 days after enrollment was high (54%) and did not differ significantly between patients who received dexamethasone (56%) and those who received placebo (53%) (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64). The rates of disability or death or clinically detectable hearing loss 1 month after enrollment or of death 6 months after enrollment were not different between the groups. Multiple subanalyses, including one subanalysis