High-Dose Fluconazole Therapy for Cryptococcal Meningitis in Patients with AIDS

Abstract

Fluconazole (800–1,000 mg iv) was administered to 14 consecutive patients with AIDS and cryptococcal meningitis. At 10 weeks the rate of clinical success was 54.5% (six of 11 patients responded to fluconazole); the Kaplan-Meier estimate of the response rate was 67.1%, and the overall mortality rate was 18.2% (two of 11 patients died). At the end of treatment, eight (72.7%) of 11 patients responded to fluconazole. The median time to the first negative cerebrospinal fluid (CSF) culture was 33.5 days (95% confidence interval, 18.3–67.3); the median time for patients with initial CSF cryptococcal antigen titers of ⩾1:1,024 was 66 days compared with 18 days for patients with initial CSF cryptococcal antigen titers of P = .06). The median time to the first negative CSF culture for patients with an isolate for which the minimum inhibitory concentration (MIC) was 4 µg/mL was 56 days compared with 16 days for patients with an isolate for which the MIC was P = .11). The mean serum and CSF levels of fluconazole at steady state were 42.47 ± 26.31 µg/mL and 36.63 ± 21.08 µlmL, respectively(ratio of CSF:serum, 0.86). No treatment was interrupted and no dose was tapered because of side effects. High-dose fluconazole might be an effective and well-tolerated therapeutic option for patients with AIDS and acute cryptococcal meningitis.