Pulmonary Aspergillosis in Mice: Treatment with a New Triazole SCH39304

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Abstract
The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis corticoid-immunosuppressed mice intranasally challenged with 5 .times. 106 conidia of Aspergillus fumigatus. In vitro, the minimum inhibitory concentration (MIC) for fluconazole was > 80 .mu.g/ml, for SCH39304 40 .mu.g/ml, and for amphotericin B 0.29 .mu.g/ml. Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses. For lung tissue counts of A. fumigatus, mice were simiarly challenged and treated only for 4 days with SCH39304, fluconazole, or amphotericin B. Only SCH39304 significantly reduced the number of A. fumigatus in the lung. SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg. Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg. SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans.

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