Efficacy of Prophylactic and Therapeutic Dosing of SCH 56592 (SCH) and Itraconazole (ITZ) against Experimental Pulmonary Asperigillosis in Mice.

D. LOEBENGERG, F. MENZEL, JR., E. CORCORAN, A.F. CACCIAPUOTI, and R.S. HARE

Abstract: 

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.
1998

abstract No: 

NULL

Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th