An infection model of pulmonary aspergillosis, similar to the clinical situation seen in neutropenic humans, was established in mice. Mice were immunocompromised with subcutaneous cortisone acetate (100 mg/kg) on days -1, 0, +1, +6, +12. Mice were infected on day 0 by exposure in inhalation flasks to spores from 13-day cultures of Aspergillus flavus and A. fumigatus. SCH, a triazole antifungal agent in phase 2 clinical trials, was administered (0.025 to 25 mq/kg) orally once daily on days -1, 0, and +1 to +7. ITZ (Sporanox(r)} solution) was administered orally (0.025 to 25 mg/kg) 3 times daily on the same days, resulting in total daily doses of 0.075 to 75 mg/kg. SCH was more efficacious than ITZ in these models. Against A. flavus, 100% of mice treated with SCH at 25 mg/kg survived to day +6, and 50% treated with 25, 10, and 5 mg/kg survived to day +18. No control or ITZ-dosed mice survived beyond day +7. Against A. fumigatus, 100% of SCH-dosed mice at 25 and 10 mg/kg, 6388% at 5 mg/kg, and 50-63% at 2.5 mg/kg, survived to day +19. Control and ITZ-dosed mice were dead by days +4 to +7.
Full conference title:
38th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 38th