In Vitro Pharmacodynamics of Amphotericin B, Itraconazole, and ...

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Apr 20, 2004 - itraconazole inhibited the growth of A. fumigatus and A. terreus isolates with MICs ... with voriconazole and amphotericin B versus itraconazole.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2005, p. 945–951 0066-4804/05/$08.00⫹0 doi:10.1128/AAC.49.3.945–951.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vol. 49, No. 3

In Vitro Pharmacodynamics of Amphotericin B, Itraconazole, and Voriconazole against Aspergillus, Fusarium, and Scedosporium spp. Russell E. Lewis,1,2* Nathan P. Wiederhold,1,2 and Michael E. Klepser3 University of Houston College of Pharmacy1 and University of Texas M. D. Anderson Cancer Center,2 Houston, Texas, and Ferris State University, Kalamazoo, Michigan3 Received 20 April 2004/Returned for modification 31 August 2004/Accepted 27 October 2004

We compared the in vitro pharmacodynamics of amphotericin B, itraconazole, and voriconazole against Aspergillus, Fusarium, and Scedosporium species with a combination of two non-culture-based techniques: the tetrazolium salt 2,3-bis-(2-methoxy-4-nitro-5-[(sulfenylamino)carbonyl]-2H-tetrazolium-hydroxide) (XTT) colorimetric reduction assay, and fluorescent microscopy with the cellular morbidity dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC) to directly visualize hyphal damage. Amphotericin B exhibited species-specific concentration-dependent activity, with 50% effective concentrations (EC50s) ranging from 0.10 to 0.12 mg/ml for A. fumigatus, 0.36 to 0.53 mg/ml for A. terreus, 0.27 to >32 mg/ml for F. solani, 0.41 to 0.55 mg/ml for F. oxysporum, and 0.97 and 0.65 mg/ml for S. apiospermum and S. prolificans, respectively. Similarly, itraconazole inhibited the growth of A. fumigatus and A. terreus isolates with MICs of