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In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole, itraconazole, posaconazole, and voriconazole.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>expressing the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>ATP binding cassette (ABC) transporters (<jats:italic>CDR1<\/jats:italic>,<jats:italic>CDR2<\/jats:italic>, and<jats:italic>CgCDR1<\/jats:italic>), major facilitator (<jats:italic>MDR1<\/jats:italic>), and lanosterol 14-\u03b1-sterol-demethylase (<jats:italic>ERG11<\/jats:italic>) alleles with mutations were used. In addition, pairs of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>strains from matched clinical isolates with known azole resistance mechanisms were investigated. The expression of ABC transporters increased all azole MICs, suggesting that all azoles tested were substrates of ABC transporters. The expression of<jats:italic>MDR1<\/jats:italic>did not increase posaconazole, itraconazole, and isavuconazole MICs. Relative increases of azole MICs (from 4- to 32-fold) were observed for fluconazole, voriconazole, and isavuconazole when at least two mutations were present in the same<jats:italic>ERG11<\/jats:italic>allele. Upon MIC testing of azoles with clinical<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>isolates with known resistance mechanisms, the MIC<jats:sub>90<\/jats:sub>s of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>for fluconazole, voriconazole, itraconazole, posaconazole, and isavuconazole were 128, 2, 1, 0.5, and 2 \u03bcg\/ml, respectively, while in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>they were 128, 2, 4, 4, and 16 \u03bcg\/ml, respectively. In conclusion, the effects of azole resistance mechanisms on isavuconazole did not differ significantly from those of other azoles. Resistance mechanisms in yeasts involving ABC transporters and<jats:italic>ERG11<\/jats:italic>decreased the activity of isavuconazole, while<jats:italic>MDR1<\/jats:italic>had limited effect.<\/jats:p>","DOI":"10.1128\/aac.02157-15","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T12:34:21Z","timestamp":1445344461000},"page":"229-238","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":70,"title":["Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms"],"prefix":"10.1128","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-4178","authenticated-orcid":false,"given":"Dominique","family":"Sanglard","sequence":"first","affiliation":[{"name":"Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix T.","family":"Coste","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/596757"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.06.012"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318206c1ca"},{"key":"e_1_3_3_5_2","first-page":"439","article-title":"Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance","volume":"3","author":"Alcazar-Fuoli L","year":"2012","unstructured":"Alcazar-Fuoli L, Mellado E. 2012. 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