title: In vitro and in vivo activities of SCH 56592 against Blastomyces dermatitidis.
abstract: 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.
authors.affiliation: Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA. asugar@med-med1.bu.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Sugar
authors.forename: X P
authors.initials: XP
authors.lastname: Liu
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001758:Blastomyces / Q000187:drug effects*; D001759:Blastomycosis / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D007928:Lethal Dose 50; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D015725:Fluconazole