Itraconazole, an orally active broad-spectrum
triazole antimycotic, has demonstrated anti-Cryptococcus activity in vitro and in animal models of
cryptococcal meningitis. The
drug has been used by a number of clinical groups for the treatment of
cryptococcal meningitis, predominantly in
AIDS patients. A problem that has been found with
ketoconazole is the relatively low absorption of the
drug in
AIDS patients. This has resulted in
ketoconazole plasma levels below the MIC90 (1-5 micrograms ml-1) needed to eliminate Cryptococcus neoformans. In addition, tissue levels of
ketoconazole are lower than plasma levels. For
itraconazole, the required MIC90 for Cr. neoformans is 0.1 microgram ml-1, and the plasma levels in
AIDS patients receiving 200-400 mg daily, even in the case of reduced absorption, are well above this MIC90. The
itraconazole levels in the brain and in the meninges are higher than the plasma levels. Consequently,
itraconazole has been considered a valid candidate for studies in patients with
cryptococcal meningitis. Various treatment modalities have been used: primary oral
therapy alone or in combination with
amphotericin B or
5-fluorocytosine (5-FC); maintenance oral
therapy after initial treatment with
amphotericin B (with or without 5-FC); and first-line intravenous treatment in severely ill patients. The results were evaluated in four different groups. When the
drug was given as primary oral
therapy without combination with
amphotericin B or 5-FC, the results depended greatly on the dose administered and on the life expectancy of the patient at inclusion. In general, daily doses of 400 mg were better than 200-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)