Suppression of Cryptococcosis and Histoplasmosis by Ketoconazole in Athymic Nude Mice

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Abstract
Congenitally athymic nude (nu/nu) mice are more susceptible to disseminated cryptococcosis and histoplasmosis than their heterozygous (nu/+) thymus-bearing littermates. The therapeutic efficacy of ketoconazole, an orally absorbable antifungal agent, was evaluated in nu/nu and nu/+ mice infected intraperitoneally with Cryptococcus neoformans and Histoplasma capsulatum, Two- to five-week courses of ketoconazole significantly prolonged the survival of nu/nu mice infected with either fungus in dosedependent fashion, but death eventually followed discontinuance of therapy. More significant protection was seen in nu/+ mice infected with C. neoformans, and markedly lower fungal counts in organs, with some negative cultures, were seen in ketoconazole-treated nu/+ mice infected with H. capsulatum, These studies indicate that ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/+ host.