Activities of the modified polyene N-D-ornithyl amphotericin methyl ester and the azoles ICI 153066, Bay n 7133, and Bay l 9139 compared with those of amphotericin B and ketoconazole in the therapy of experimental blastomycosis

Abstract

We studied the efficacy of new experimental antifungal drugs, which represent molecular modifications of present active agents, in a murine model of blastomycosis. Ketoconazole, previously the best azole drug studied and which is protective when administered orally, was superior to a new oral imidazole, Bay l 9139, and a new oral triazole, Bay n 7133. A new oral triazole, ICI 153066, was markedly more effective than ketoconazole and is the only oral drug studied which came close to producing complete sterilization of all visceral infection in all animals treated. Amphotericin B, a polyene given parenterally, was shown to be more efficacious than any drug studied. It completely sterilized the infection. A modified polyene, N-D-ornithyl amphotericin methyl ester, was only slightly less effective on a milligram-per-kilogram basis.