title: In vitro and in vivo activities of posaconazole against Coccidioides immitis.
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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases (7881) , The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. gmglez@yahoo.com.mx
authors.forename: Gloria M
authors.initials: GM
authors.lastname: González
authors.forename: Rolando
authors.initials: R
authors.lastname: Tijerina
authors.forename: Laura K
authors.initials: LK
authors.lastname: Najvar
authors.forename: Rosie
authors.initials: R
authors.lastname: Bocanegra
authors.forename: Michael
authors.initials: M
authors.lastname: Rinaldi
authors.forename: David
authors.initials: D
authors.lastname: Loebenberg
authors.forename: John R
authors.initials: JR
authors.lastname: Graybill
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D003045:Coccidioides / Q000187:drug effects* / Q000302:isolation & purification; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D004195:Disease Models, Animal; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole