In Vitro and In Vivo Activities of Posaconazole against Coccidioides immitis

Posaconazole (SCH 56592) was tested against 25 strains of Coccidioides immitis to determine their in vitro susceptibilities. The geometric mean 48-h MIC of posaconazole (POSA) was 0.5 μg/ml, the MIC range was 0.25 to 1 μg/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC(50)) and the MIC(90) were 0.5 and 1 μg/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 μg/ml, the MIC range was 0.125 to 0.5 μg/ml, and the MIC(50) and MIC(90) were both 0.25 μg/ml. Two strains of C. immitis were selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates. POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day was compared with ITRA administered at 10 and 30 mg/kg three times a day. The spleens and livers of mice that died or survived to day 50 were removed to measure the fungal burdens. Mice had ≥90% survival when they were treated with ≥0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and livers from mice treated with 10 mg of POSA per kg showed ≥70% sterilization. No sterilization of whole spleens and livers from mice treated with ITRA was seen. POSA displayed potent in vivo activity against the two strains of C. immitis tested.