Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome

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Abstract

objective: To assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS).

design: Retrospective, nonrandomized, open trial.

setting: Multicenter at two university referral centers and in five private practices.

patients: Seventy-six patients with AIDS and disseminated histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluconazole to prevent relapse.

interventions: Fluconazole was given at dosages of 100 to 400 mg per day. Patients were followed by their primary physicians, who completed questionnaires collecting information about treatment and relapse status. Blood and urine specimens were submitted periodically for Histoplasma capsulatum var. capsulatum antigen determination.

measurements and main results: Nine of the 76 patients relapsed during fluconazole therapy and another was removed from the study because of allergic rash. Survival after initiation of therapy for histoplasmosis was 94 weeks, ranging from 74 weeks for those who received less than 1 g of amphotericin B for induction and none for maintenance therapy to 156 weeks for those who received greater than 1 g for induction and additional amphotericin B for maintenance therapy before beginning fluconazole (P < 0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by ≥2 units/week in 4 of 6 patients who relapsed.

conclusions: Fluconazole ≥200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who cannot take itraconazole because of drug interactions, malabsorption, or side effects.

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