[Anti-Candida activity of azoles]

Abstract

The in vitro activity of the broad-spectrum antifungals miconazole, ketoconazole and itraconazole was evaluated by the decimal dilution method in liquid media, for respectively 2511, 1536 and 1859 strains of yeasts belonging to 31 species. Sabouraud broth was used for miconazole and brain heart infusion broth for ketoconazole and itraconazole. These three azoles proved to be potent anti-yeast compounds. Activity by oral treatment of miconazole, ketoconazole and itraconazole was compared in gastro-intestinal candidosis of the guinea-pig, in vaginal candidosis of the rat and in systemic candidosis of the guinea-pig. Ketoconazole and itraconazole are more efficacious than miconazole in gastro-intestinal candidosis. Miconazole showed marginal activity in the other two experimental models: the spectrum of activity of miconazole was a lead for research which resulted in the synthesis and selection of ketoconazole and itraconazole. Ketoconazole was highly active in these experimental models. Itraconazole cured the animals at distinctly lower doses. No side-effects due to these azoles were observed during these experiments. A proposal is made to classify the broad-spectrum azoles in three classes: compounds for topical use (e.g. miconazole), compounds with oral activity without activity in aspergillosis (e.g. ketoconazole), compounds with oral activity including activity in aspergillosis (e.g. itraconazole).