High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS.
Fluconazole (800-1,000 mg i.v.) 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 > or = 1:1,024 was 66 days compared with 18 days for patients with initial CSF cryptococcal antigen titers of < 1:1,024 (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 micrograms/mL was 56 days compared with 16 days for patients with an isolate for which the MIC was < 4 micrograms/mL (P = .11). The mean serum and CSF levels of fluconazole at steady state were 42.47 +/- 26.31 micrograms/mL and 36.63 +/- 21.08 micrograms/mL, 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.
Menichetti
F
F
Institute of Infectious Diseases, University of Perugia, Italy.
Fiorio
M
M
Tosti
A
A
Gatti
G
G
Bruna Pasticci
M
M
Miletich
F
F
Marroni
M
M
Bassetti
D
D
Pauluzzi
S
S
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000946:Antigens, Fungal / Q000097:blood / Q000134:cerebrospinal fluid; D003454:Cryptococcus / Q000276:immunology / Q000302:isolation & purification; D004361:Drug Tolerance; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology; D008875:Middle Aged; D013997:Time Factors
D000935:Antifungal Agents; D000946:Antigens, Fungal; D015725:Fluconazole