HIGH-DOSE FLUCONAZOLE FOR TREATMENT OF CRYPTOCOCCAL DISEASE IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Eight patients (6, cryptococcal meningitis; 2, high-titer cryptococcal antigenemia) were treated with 800 mg/day fluconazole to assess the safety and efficacy of high-dose fluconazole as primary therapy. Five patients with meningitis had resolution of clinical symptoms and all 6 had negative cerebrospinal fluid (CSF) cultures by day 82 (median, 21 days). One meningitis patient developed neurologic deterioration and was switched to amphotericin B at day 18, but CSF culture was negative on day 15 of fluconazole therapy. In 2 patients with cryptococcal antigenemia, clinical symptoms resolved and serum antigen titers declined rapidly; they did not progress to meningitis. Therapy was well tolerated, with mainly gastrointestinal side effects. Four patients had mild increases in liver enzymes; another had a threefold increase in alkaline phosphatase. Mean steady-state serum level of fluconazole was 45 +/- 15 mu g/mL, and paired CSF and serum levels were 40 +/- 14 and 49 +/- 14 mu g/mL, respectively. High-dose fluconazole appears safe and effective for cryptococcal disease in AIDS patients.