In Vitro Antifungal Activity of Isavuconazole (BAL4815),

35 36 Isavuconazole (BAL4815) is a promising novel broad-spectrum triazole in late37 stage clinical development that has proven active in vitro against Aspergillus and 38 Candida. We compared the in vitro activity of this agent with that of voriconazole and 39 fluconazole by the CLSI M38-A and CLSI M27-A2 procedures against a large 40 collection of 1007 relevant opportunistic fungi collected from 1986 to 2007: 41 Aspergillus spp. (702), Candida spp. (218), Zygomycetes (45), Scedosporium spp. 42 (22), and Fusarium spp. (20). All isolates of Candida were from patients with 43 candidemia. For isavuconazole, these techniques were also compared with the E44 test. Isavuconazole and voriconazole showed an MIC50/MIC90, respectively, of 1/1 45 μg/mL and 0.5/1 μg/mL against Aspergillus spp., and 0.015/0.25 μg/mL and 46 0.03/0.125 μg/mL against Candida spp. (including fluconazole-resistant strains). The 47 MIC50 partial/complete inhibition endpoints of isavuconazole and voriconazole against 48 the non-Aspergillus molds were as follows: 1/2 μg/mL and 16/>16 μg/mL against 49 Zygomycetes; 1/4 μg/mL and 0.25/0.5 μg/mL against S. apiospermum; 4-16/>16 50 μg/mL and 4-8/16->16 μg/mL (ranges) against S. prolificans; and 16/16 and 4/4 51 μg/mL against Fusarium spp. Isavuconazole showed an MFC50/MFC90 of 1/1 μg/mL 52 against Aspergillus, 0.5/16 μg/mL against Candida, 4/>16 μg/mL against 53 Zygomycetes and >16 μg/mL against the remaining molds. The E-test proved to be a 54 suitable alternative method for determining the antifungal activity of isavuconazole 55 against Aspergillus, and Candida, with an agreement between CLSI M38-A and CLSI 56 M27-A2 and the E-test of 96% and 93%, respectively. 57 AC EP TE D on July 5, 2017 by gest httpaac.asm .rg/ D ow nladed fom INTRODUCTION 58 59 Invasive fungal infections (IFIs) are an important and increasing cause of morbidity 60 and mortality in immunocompromised populations (6, 7). Despite correct antifungal 61 treatment with available agents, the mortality rate of patients with IFIs remains 62