HIGH-DOSE FLUCONAZOLE THERAPY FOR CRYPTOCOCCAL MENINGITIS IN PATIENTSWITH AIDS

Fluconazole (800-1,000 mg iv) was administered to 14 consecutive patie nts with AIDS and cryptococcal meningitis, At 10 weeks the rate of cli nical success was 54.5% (six of 11 patients responded to fluconazole); the Kaplan-Meier estimate of the response rate was 67.1%, and the ove rall 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 w as 33.5 days (95% confidence interval, 18.3-67.3); the median time for patients with initial CSF cryptococcal antigen titers of greater than or equal to 1:1,024 was 66 days compared with 18 days for patients wi th initial CSF cryptococcal antigen titers of <1:1,024 (P = .06), The median time to the first negative CSF culture for patients with an iso late for which the minimum inhibitory concentration (MIC) was 4 mu g/m L was 56 days compared with 16 days for patients with an isolate for w hich the MIC was <4 mu g/mL (P = .11), The mean serum and CSF levels o f fluconazole at steady state were 42.47 +/- 26.31 mu g/mL and 36.63 /- 21.08 mu g/mL, respectively (ratio of CSF:serum, 0.86), No treatmen t was interrupted and no dose was tapered because of side effects. Hig h-dose fluconazole might be an effective and well-tolerated therapeuti c option for patients with AIDS and acute cryptococcal meningitis.