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Antimicrob. Agents Chemother. doi:10.1128/AAC.01512-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In Vitro Antifungal Activity of Isavuconazole (BAL4815), Voriconazole, and Fluconazole Against 1007 Isolates of Zygomycetes, Candida, Aspergillus, Fusarium, and Scedosporium Species

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario "Gregorio Marañón", Universidad Complutense de Madrid, Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBER RES CD06/06/0058

^* To whom correspondence should be addressed. Email: jguineaortega{at}yahoo.es.

	Abstract

Isavuconazole (BAL4815) is a promising novel broad-spectrum triazole in late-stage clinical development that has proven active in vitro against Aspergillus and Candida. We compared the in vitro activity of this agent with that of voriconazole and fluconazole by the CLSI M38-A and CLSI M27-A2 procedures against a large collection of 1007 relevant opportunistic fungi collected from 1986 to 2007: Aspergillus spp (702)., Candida spp. (218), Zygomycetes (45), Scedosporium spp. (22), and Fusarium spp. (20). All isolates of Candida were from patients with candidemia. For isavuconazole, these techniques were also compared with the E-test. Isavuconazole and voriconazole showed an MIC₅₀/MIC₉₀, respectively, of 1/1 µg/mL and 0.5/1 µg/mL against Aspergillus spp., and 0.015/0.25 µg/mL and 0.03/0.125 µg/mL against Candida spp. (including fluconazole-resistant strains). The MIC₅₀ partial/complete inhibition endpoints of isavuconazole and voriconazole against the non-Aspergillus molds were as follows: 1/2 µg/mL and 16/>16 µg/mL against Zygomycetes; 1/4 µg/mL and 0.25/0.5 µg/mL against S. apiospermum; 4-16/>16 µg/mL and 4-8/16->16 µg/mL (ranges) against S. prolificans; and 16/16 and 4/4 µg/mL against Fusarium spp. Isavuconazole showed an MFC₅₀/MFC₉₀ of 1/1 µg/mL against Aspergillus, 0.5/16 µg/mL against Candida, 4/>16 µg/mL against Zygomycetes and >16 µg/mL against the remaining molds. The E-test proved to be a suitable alternative method for determining the antifungal activity of isavuconazole against Aspergillus, and Candida, with an agreement between CLSI M38-A and CLSI M27-A2 and the E-test of 96% and 93%, respectively.