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Antimicrobial Agents and Chemotherapy, March 2004, p. 758-764, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.758-764.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activity of Posaconazole Combined with Amphotericin B against Aspergillus flavus Infection in Mice: Comparative Studies in Two Laboratories

Laura K. Najvar,1* Anthony Cacciapuoti,2 Steve Hernandez,1 Judith Halpern,2 Rosie Bocanegra,1 Maya Gurnani,2 Frederick Menzel,2 David Loebenberg,2 and John R. Graybill1

Department of Medicine, Division of Infectious Disease, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900,1 Schering Plough Research Institute, Kenilworth, New Jersey 07033-13002

Received 12 June 2003/ Returned for modification 29 July 2003/ Accepted 12 November 2003

Posaconazole and/or amphotericin B was given to mice pretreated with a steroid and then infected by inhalation of Aspergillus flavus conidia. Two laboratories conducted studies using almost identical protocols to evaluate both survival and lung tissue burdens 8 days after infection. The results of the in vivo studies performed at both laboratories were consistent. We found that (i) up to 5 mg of amphotericin B per kg of body weight was poorly effective in treating invasive aspergillosis; (ii) posaconazole at 2 or 10 mg/kg/dose prolonged survival and reduced lung tissue CFU; and (iii) there was generally no antagonistic interaction of the drugs in combination, even when the experiments were designed to maximize the likelihood of antagonism. These studies do not confirm the antagonistic interaction of triazoles and polyenes reported by others.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Disease (7881), The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. Phone: (210) 567-0990. Fax: (210) 567-0962. E-mail: Najvar{at}uthscsa.edu.

Antimicrobial Agents and Chemotherapy, March 2004, p. 758-764, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.758-764.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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