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Table 1 summarizes the MIC distributions and in vitro susceptibilities of 296 bloodstream isolates of Candida spp. to isavuconazole in comparison to other azole antifungal agents, amphotericin B and flucytosine. Isavuconazole showed good activity against all Candida spp., including those species that are inherently less susceptible to fluconazole, e.g. C. glabrata and C. krusei. Overall, on the basis of MIC90s, isavuconazole was as active as amphotericin B, itraconazole and voriconazole each, 0.5 mg L ; , and more active than flucytosine 2 mg L ; and fluconazole 8 mg L ; . In terms of MIC50s, isavuconazole was more active 0.004 mg L ; than amphotericin B 0.5 mg L ; , itraconazole 0.008 mg L ; , voriconazole 0.03 mg L ; , flucytosine 0.125 mg L ; , and fluconazole 8 mg L ; . For isavuconazole, MIC50s MIC90s ranged from 0.002 0.004 mg L for C. albicans to 0.25 0.5 mg L for C. glabrata. Using tentative breakpoints, all isolates were susceptible to amphotericin B, whereas 92.6% of isolates were susceptible to flucytosine. Non-susceptibility to 5.

Clinical isolates belonging to six of the most common species of dermatophytes were tested Table 1 ; . Paecilomyces variotii ATCC 36257 was included as a reference strain. The fungi were subcultured on potato dextrose agar, and stock inoculum suspensions were prepared according to the recommendations of the NCCLS 13 ; . This suspension was then adjusted with a spectrophotometer to 65 to 70% transmittance for dermatophytes and to 74 to 76% transmittance for P. variotii at a wavelength of 530 nm. The working suspension was made by dilution of the suspensions 1: 100 in RPMI 1640 to produce the final test concentration of the inoculum. Aliquots of 100 l of the diluted suspension were inoculated into the wells with antifungals and the growth control well containing only diluent and colorimetric indicator ; with a multichannel pipette. The concentrations of the amphotericin B, itraconazole, and ketoconazole dilutions ranged from 0.008 to 16 g ml, and the concentrations of the fluconazole dilutions ranged from 0.12 to 256 g ml. Flucytosine was not evaluated, as in previous studies the MICs of this drug for these fungi were very high. The panels were incubated at 28C until a change in color from blue indicative of no growth ; to red indicative of growth ; was observed in the growth control well. The MIC of amphotericin B was defined as the lowest drug concentration which prevented the development of a red color the first blue well ; . For the rest of the antifungals tested, the same criterion was applied, but when a purple color remained during a change from red to blue indicative of partial growth inhibition ; , the MIC was defined as the lowest drug concentration which resulted in a purple color. Broth microdilution method. The broth microdilution method described previously 8 ; was an adaptation of the method recommended by the NCCLS 13 ; for the testing of dermatophytes. The inoculum was prepared and standardized spectrophotometrically as described above for the method with the Sensititre YeastOne panel. Eleven dilutions of each drug were tested, i.e., concentrations of 0.01 to 16 g for amphotericin B, itraconazole, and ketoconazole and concentrations of 0.12 to 128 g ml for fluconazole. The microdilution plates were incubated at 28C. The amphotericin B MIC was defined as the lowest drug concentration at which there was no growth. The azole MICs were defined as the lowest drug con.

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