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Antimicrobial Agents and Chemotherapy, March 2005, p. 945-951, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.945-951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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 Pharmacy,1 University of Texas M. D. Anderson Cancer Center, Houston, Texas,2 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 <1 mg/ml (EC50 0.03 to 0.85 mg/ml) and S. apiospermum, but was not active against Fusarium species or S. prolificans. Voriconazole effectively inhibited the growth of Aspergillus, Fusarium, and S. apiospermum (EC50 0.10 to 3.3 mg/ml) but had minimal activity against a multidrug-resistant isolate of F. solani or S. prolificans. Hyphal damage visualized by DiBAC staining was observed more frequently with voriconazole and amphotericin B versus itraconazole. These data highlight the species-specific differences in antifungal pharmacodynamics between mold-active agents that could be relevant for the development of in vitro susceptibility breakpoints and antifungal dosing in vivo.

* Corresponding author. Mailing address: University of Houston College of Pharmacy, 1441 Moursund St. #423, Houston, TX 77030. Phone: (713) 795-8326. Fax: (713) 795-8383. E-mail: rlewis{at}uh.edu.

Antimicrobial Agents and Chemotherapy, March 2005, p. 945-951, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.945-951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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