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Antimicrobial Agents and Chemotherapy, May 2002, p. 1352-1356, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1352-1356.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of Posaconazole against Coccidioides immitis

Gloria M. González,1,2* Rolando Tijerina,2 Laura K. Najvar,1 Rosie Bocanegra,1 Michael Rinaldi,3,4 David Loebenberg,5 and John R. Graybill1

Department of Medicine, Division of Infectious Diseases (7881),1 Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900,3 Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México,2 Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, Texas 78224,4 Schering-Plough Research Institute, Kenilworth, New Jersey 07033-05305

Received 19 July 2001/ Returned for modification 10 September 2001/ Accepted 4 February 2002

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 (MIC50) and the MIC90 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 MIC50 and MIC90 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.

* Corresponding author. Mailing address: Facultad de Medicina, Universidad Autónoma de Nuevo León, Departamento de Microbiología, Madero y Dr. Eduardo A. Pequeño s/n, Colonia Mitras Centro, Monterrey, N.L. 64460, Mexico. Phone: (52) 8329 4166. Fax: (52) 8348 5477. E-mail: gmglez{at}yahoo.com.mx.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1352-1356, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1352-1356.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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