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Study of Current and New Drugs in a Murine Model of Acute Paracoccidioidomycosis^*

Eli Lefler, Elmer Brummer, Juan G. McEwen^,,, Guillermo L. Hoyos^,,, Angela Restrepo AND David A. Stevens

Division of Infectious Diseases, Department of Medicine and Clinical Microbiology Laboratory, Department of Pathology, Santa Clara Valley Medical Center, Stanford University, and Institute for Medical Research, San Jose, California 95128
Laboratory of Mycology, Corporacion de Investigaciones Biológicas, Hospital Pablo Tobon Uribe, Medellín, Colombia

A new murine model of acute paracoccidioidomycosis, whose features include pulmonary infection with dissemination, was used to study the efficacy of currently available drugs and new agents which might be useful clinically. Two oral imidazole drugs, ketoconazole (KTZ) and Bay l 9139 (l9); two oral triazoles, Bay n 7133 (n7) and ICI 153,066 (ICI); and two polyenes, amphotericin B (AMB) and N-D-ornithyl-amphotericin B methyl ester, were studied. KTZ was superior to n7 and l9, particularly after a less lethal challenge. The polyenes could diminish dissemination, but had only modest effects on the pulmonary infection; AMB appeared slightly more effective. ICI was the most effective drug studied, approximately 5–10 times more potent than KTZ on a milligram/kg body weight basis; it had marked effects on both pulmonary and disseminated disease. These initial applications of the model to therapeutic evaluation suggest sufficient flexibility and utility, with information obtainable after relatively short experiments.

Accepted for publication June 21, 1984.

^* Address reprint requests to: Dr. D. A. Stevens, Department of Medicine, Santa Clara Valley Medical Center, 751 So. Bascom Avenue, San Jose, California 95128.