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Antimicrobial Agents and Chemotherapy, 05 1996, 1314-1316, Vol 40, No. 5
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

In vitro and in vivo activities of SCH 56592 against Blastomyces dermatitidis

AM Sugar and XP Liu
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA. asugar@med-med1.bu.edu

The new triazole derivative SCH 56592 has been tested in a National Committee for Clinical Laboratory Standards-adapted in vitro susceptibility test, and its activity against 12 isolates of Blastomyces dermatitidis yeast-like forms has been compared with those of amphotericin B, itraconazole, and fluconazole. SCH 56592 was the most active of the four compounds, with an MIC at which 90% of the isolates are inhibited of 0.06 microgram/ml and a minimal fungicidal concentration at which 90% of the isolates are inhibited of 4 micrograms/ml. The results of the treatment of mice infected with B. dermatitidis with three different doses of SCH 56592 (25, 5, or 1 mg/kg of body weight), amphotericin B (1 mg/kg), or itraconazole (150 mg/kg) confirmed the potent activity of SCH 56592. Survival was prolonged at each dose of SCH 56592, and sterilization of the lungs occurred in the high-dose group but not in the groups treated with itraconazole or fluconazole. SCH 56592 is a promising new azole antifungal drug that should be studied in humans with blastomycosis.


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