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In a study conducted in Vietnam, Dr. Jeremy J. Farrar and colleagues show that dexamethasone is only effective if given to patients with confirmed bacterial meningitis, not to those with probable disease. In fact, giving the drug to patients with probable disease seemed to increase the risk of death at 1 month.
The findings from the second study, conducted in a sub-Saharan African city with a high HIV prevalence, indicated little or no benefit of using the corticosteroid for this indication. The results of both studies are reported in The New England Journal of Medicine for December 13th.
"Dexamethasone is a very, very cheap drug and probably because there is no industry interest there has remained a question for more than 30 years as to whether it reduces mortality in patients with meningitis," Dr. Farrar, from the John Radcliffe Hospital in Oxford, UK, told Reuters Health.
The results of this study indicate that the drug can produce a "major" reduction in morbidity and mortality if the patient has confirmed disease, Dr. Farrar said.
This last part is important, he emphasized, because in the developing world, TB meningitis is fairly common and can mimic bacterial meningitis, which refers to meningitis caused by non-TB bacteria, usually Streptococcus pneumoniae or Neisseria meningitidis.
The study involved 435 adolescents and adults with suspected bacterial meningitis who were randomized to receive intravenous dexamethasone or placebo for 4 days in addition to a 10- to 14-day course of ceftriaxone. Some of the patients had received antibiotics before inclusion in the study. All of the patients were HIV-negative.
Sixty-nine percent of patients had confirmed bacterial meningitis, 28.3% had probable meningitis, and 2.8% had an alternative diagnosis.
In the overall analysis, dexamethasone therapy did not reduce mortality at 1 month or the risk of death or disability at 6 months. When the analysis was confined to patients with confirmed bacterial meningitis, however, use of the drug reduced 1-month mortality by 57% and the 6-month risk of death or disability by 44%.
As noted, use of dexamethasone for probable bacterial meningitis appeared to increase the risk of death at 1 month. The researchers believe that this is because many of the cases of probable bacterial meningitis actually had TB meningitis, which responded adversely to the drug.
"From this study, if you have an adult patient who is HIV-negative, in whom you confirm acute bacterial meningitis, you should give steroids, even if the patient has had antibiotics before coming to the hospital," Dr. Farrar said. "It also shows how important good diagnostic laboratories are and that by having good laboratories making a quick diagnosis, you can reduce death by a half."
In the second study, which was centered in Blantyre, Malawi, Dr. Matthew Scarborough, also from the John Radcliffe Hospital in Oxford, UK, and colleagues assessed the outcomes of 465 patients who were admitted with bacterial meningitis and randomized to receive intravenous dexamethasone or placebo in combination with intramuscular or intravenous ceftriaxone. In contrast to the first study, 90% of the subjects were HIV-positive.
Dexamethasone therapy did not reduce morbidity or mortality in the study group. Ceftriaxone efficacy was not significantly influenced by its route of administration.
"This trial does not provide support for the routine inclusion of corticosteroids in the management of adult bacterial meningitis in resource-poor areas where pneumococcus is the primary pathogen and where a substantial proportion of patients are likely to have advanced HIV disease," the authors conclude.