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. 2002 May;46(5):1352-6.
doi: 10.1128/AAC.46.5.1352-1356.2002.

In vitro and in vivo activities of posaconazole against Coccidioides immitis

Gloria M González  1 , Rolando Tijerina, Laura K Najvar, Rosie Bocanegra, Michael Rinaldi, David Loebenberg, John R Graybill
Affiliations

In vitro and in vivo activities of posaconazole against Coccidioides immitis

Gloria M González et al. Antimicrob Agents Chemother. 2002 May.

Abstract

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 microg/ml, the MIC range was 0.25 to 1 microg/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC50) and the MIC90 were 0.5 and 1 microg/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 microg/ml, the MIC range was 0.125 to 0.5 microg/ml, and the MIC50 and MIC90 were both 0.25 microg/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 >or=90% survival when they were treated with >or=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 >or=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.

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Figures

FIG. 1.
FIG. 1.
Survival study after intravenous infection with 200 arthroconidia of C. immitis strain 97-960 (MIC, 0.25 μg/ml). Therapy was given on days 2 to 22 after infection. The control group received sterile distilled water. There were 10 animals per group. The survivors were killed on day 50. TID, three times a day.
FIG. 2.
FIG. 2.
Survival study after intravenous infection with 200 arthroconidia of C. immitis strain 97-2036 (MIC, 1 μg/ml). Therapy was given on days 2 to 22 after infection. The control group received sterile distilled water. There were 10 animals per group. The survivors were killed on day 50. TID, three times a day.
See this image and copyright information in PMC

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