In vitro and in vivo studies of ambruticin (W7783): new class of antifungal antibiotics

Abstract

Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 mug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 mug/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 mug/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.