In vitro antifungal spectrum of itraconazole and treatment of systemic mycoses with old and new antimycotic agents

Abstract

Itraconazole is a lipophilic triazole with potent in vitro activity. It is also effective after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth). Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp. (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C. albicans, Cr. neoformans, Histoplasma duboisii, S. schenckii, P. marneffei and A. fumigatus. It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies have yet been undertaken for other deep mycoses. The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.