Suppression of cryptococcosis and histoplasmosis by ketoconazole in athymic nude mice.
Congenitally athymic nude (nu/nu) mice are more susceptible to disseminated cryptococcosis and histoplasmosis than their heterozygous (nu/ + ) thymus-bearing litter-mates. 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 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. These studies indicate that ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/ + host.
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000401:mortality / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000472:pathogenicity; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006658:Histoplasma / Q000187:drug effects* / Q000472:pathogenicity; D006660:Histoplasmosis / Q000401:mortality / Q000517:prevention & control*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007108:Immune Tolerance; D051379:Mice; D008819:Mice, Nude / Q000502:physiology*; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D007093:Imidazoles