Role of fluconazole in the management of AIDS-related cryptococcosis, according to daily dosing

No unanimous consent has been reached about treatment guidelines of cryptococcosis in the setting of AIDS, as well as about optimal fluconazole dosing in both initial and suppressive therapy. In order to evaluate the relationship between fluconazole dosing and clinical and microbiological outcome of AIDS-related cryptococcosis, a retrospective study was carried out on 30 consecutive patients. Among the 12 subjects treated with fluconazole doses <400 mg/day, an unfavorable course was significantly more frequent (early mortality, poor clinical and microbiological response, appearance of early relapses) compared with the 18 patients who received daily doses greater than or equal to 400 mg, while no differences were observed between the two treatment groups according to known risk factors for a poor prognosis. When assessing maintenance treatment (22 evaluable cases), the 15 patients receiving oral fluconazole at doses <200 mg/day showed earlier disease relapse and mortality as opposed to the 7 individuals treated with high-dose fluconazole (greater than or equal to 200 mg/day), in the absence of significantly different risk factors for disease recurrence. Our experience pointed out a significant difference in clinical activity of fluconazole in AIDS-related cryptococcosis according to its daily dosing, and suggested 400 and 200 mg as the threshold daily dose for an effective initial and suppressive therapy, respectively, since the probability of treatment failure seemed greater with low-dose drug administration, after controlling data for prognostic markers of disease severity. Controlled studies are warranted, comparing high-dose fluconazole with standard regimens containing amphotericin B in the treatment of AIDS-associated cryptococcosis, and identifying the best fluconazole dosing for both acute-phase and maintenance treatment.