SCH-39304 IN THE TREATMENT OF ACUTE OR ESTABLISHED MURINE PULMONARY BLASTOMYCOSIS

SCH 39304 was tested for treatment of acute or established murine pulmonary blastomycosis and was compared with ketoconazole and fluconazole in a model of acute infection. Only SCH 39304 at 25 or 50 mg/kg of body weight per day produced 100% survival for 30 days after the 20-day treatment, although only 33% of the mice were cleared of infection. SCH 39304 at 2 mg/kg/day was similar to ketoconazole at 100 mg/kg/day and to fluconazole at 10 mg/kg/day. In a model of established blastomycosis, used to evaluate long-term treatment of very sick or moribund mice, SCH 39304 at 50 mg/kg/day protected against death with a 96% cumulative 8-week survival. SCH 39304 was clearly superior on a milligram-per-kilogram basis in acute blastomycosis, and long-term treatment of more severe blastomycosis was curative.