Fungistatic and fungicidal effects of amphotericin B, ketoconazole and fluconazole (UK 49,858) against histoplasma capsulatum in vitro and in vivo.

Abstract

Summary: Amphotericin B (Amph B), ketoconazole (KTZ) and fluconazole (FLZ) were compared for activity against yeast phase H. capsulatum in vitro and in Swiss albino mice. A quantitative spleen culture technique for yeast phase colony forming units (CFU) was used to evaluate the antifungal effects of these 3 drugs in vivo. In contrast to the in vitro indications, all 3 drugs showed fungicidal activity as demonstrated by the exponential decreases in CFU from spleens of infected mice. When relating the fungicidal activity obtained by this technique to the ED50 or ED100 values, KTZ and FTZ appeared to be the most active drugs. Fluconazole compared favorably to KTZ. At twice the ED100 Amph B had no significant effect upon viable yeasts recovered until after day 3 or infection (p ≤ 0.01). Thereafter, the drug was fungicidal. Based upon these studies, FLZ would appear to hold promise in the clinical management of histoplasmosis.