Fluconazole for AIDS-related cryptococcal meningitis

Date: May, 1992

Cryptococcal meningitis is the most common life-threatening opportunistic fungal disease in patients infected with the human immunodeficiency virus (HIV). It occurs in 5 to 8 percent of patients with acquired immunodeficiency syndrome. Intravenous amphotericin B, with or without flucytosine, is the standard treatment for these patients. However, the success rate of this treatment is only 40 to 50 percent, and drug intolerance is common. Saag and colleagues conducted a randomized, multicenter, clinical trial to compare the efficacy of intravenous amphotericin B with oral fluconazole in the treatment of cryptococcal meningitis in patients with AIDS. Fluconazole is a new antifungal agent that is highly active against Cryptococcus neoformans infection induced in animals.

The study included 194 patients with cryptococcal meningitis. A total of 131 patients were randomized to receive fluconazole, a single 400-mg oral loading dose on the first day and 200 mg daily thereafter. Sixty-three patients were randomized to receive amphotericin B intravenously in a dose of at least 0.3 mg per kg per day or in an equivalent dose given every other day. Treatment was considered successful if the patient had clinical improvement or complete resolution of symptoms together with two consecutive negative cultures of cerebrospinal fluid samples obtained at least one week apart. Twenty-five (40 percent) of the patients receiving amphotericin B were treated successfully, compared with 44 (34 percent) of the patients receiving fluconazole. The first negative cerebrospinal fluid culture was taken after an average of 42 days in the amphotericin B group, compared with. 64 days in the fluconazole group.

Although more deaths occurred in the first two weeks of therapy in the fluconazole group than in the amphotericin group (18 percent versus 14 percent), the two groups demonstrated no differences in overall mortality associated with progressive cryptococcal disease. Patients with lethargy, obtundation or other abnormal mental status findings were at significantly higher risk for death despite therapy.

The study indicates that fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. While single-agent therapy with either drug is effective in patients at low risk for treatment failure, the optimal approach for patients at higher risk requires further study. (New England Journal of Medicine, January 9, 1992, vol. 326, p. 83. )

COPYRIGHT 1992 American Academy of Family PhysiciansCOPYRIGHT 2004 Gale Group

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