Suppression of Cryptococcosis and Histoplasmosis by Ketoconazole in Athymic Nude Mice

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 antifugal agent, was evaluated in nu/nu and nu/+ mice infected i.p. 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 a dose-dependent 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. Ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/+ host.