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 micrograms/mL, and paired CSF and serum levels were 40 +/- 14 and 49 +/- 14 micrograms/mL, respectively. High-dose
fluconazole appears safe and effective for cryptococcal disease in
AIDS patients.