Combination therapy of experimental histoplasmosis and cryptococcosis with amphotericin B and ketoconazole.
Combinations of amphotericin B and ketoconazole had an additive effect in vitro against Histoplasma capsulatum and Cryptococcus neoformans; ketoconazole combined with flucytosine exerted an indifferent effect against C. neoformans. In vivo studies in athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates demonstrated that treatment with the ketoconazole-amphotericin B combination resulted in longer survival of mice with cryptococcosis than did treatment with ketoconazole plus flucytosine. However, mice given ketoconazole plus amphotericin B did not survive significantly longer than those given amphotericin B alone (cryptococcosis) or ketoconazole alone (histoplasmosis). Combination chemotherapy with ketoconazole and amphotericin B may offer a modest therapeutic advantage over therapy with either drug alone.
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000254:growth & development; D004359:Drug Therapy, Combination; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use; D006658:Histoplasma / Q000254:growth & development; D006660:Histoplasmosis / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D007654:Ketoconazole; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010879:Piperazines / Q000627:therapeutic use*
D007093:Imidazoles; D010879:Piperazines; D000666:Amphotericin B; D005437:Flucytosine; D007654:Ketoconazole