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Antimicrobial Agents and Chemotherapy, June 2006, p. 2009-2015, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00163-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts

F. Sabatelli, R. Patel, P. A. Mann, C. A. Mendrick, C. C. Norris, R. Hare, D. Loebenberg, T. A. Black, and P. M. McNicholas*

Schering-Plough Research Institute, Kenilworth, New Jersey

Received 7 February 2006/ Returned for modification 1 March 2006/ Accepted 1 April 2006

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC50 and MIC90 values for posaconazole were 0.063 µg/ml and 1 µg/ml, respectively. MIC90 values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 µg/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.

* Corresponding author. Mailing address: Schering-Plough Research Institute, 2015 Galloping Hill Road (K15-4-4700), Kenilworth, NJ 07033. Phone: (908) 740-7644. Fax: (908) 740-3918. E-mail: paul.mcnicholas{at}spcorp.com.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2009-2015, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00163-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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