FLUCONAZOLE COMBINED WITH FLUCYTOSINE FOR TREATMENT OF CRYPTOCOCCAL MENINGITIS IN PATIENTS WITH AIDS

Treatment of cryptococcal meningitis with amphotericin B or fluconazol e is often unsuccessful; in only 35%-40% of cases do CSF cultures beco me negative by 10 weeks after initiation of such therapy. We conducted a prospective, open-label clinical trial involving persons with AIDS to determine whether the rate of clinical success would improve when f luconazole (400 mg daily) was combined with flucytosine (150 mg/kg dai ly). At the conclusion of 10 weeks of therapy, 75% (95% confidence int erval, 58%-87%) of 32 subjects' CSF cultures were negative. The Kaplan -Meier estimate of clinical success at 10 weeks was 63% (95% confidenc e interval, 48%-82%). The median time to negativity of the CSF culture was 23 days. Toxic side effects that were sufficiently severe to lead to the withdrawal of flucytosine were observed in nine subjects (28%) . In this pilot study of fluconazole combined with flucytosine, the ra te of clinical success at 10 weeks was greater than that previously re ported with regard to the use of fluconazole alone or amphotericin B a lone.