EUCAST Susceptibility Testing of Isavuconazole: MIC Data for Contemporary Clinical Mold and Yeast Isolates

Isavuconazole is the newest medical azole. We investigated EUCAST MICs for isavuconazole and seven comparators against 1,498 contemporary isolates (2016 to 2017). EUCAST susceptibility testing was performed. Isavuconazole MICs >2 dilution steps above the modal MIC were regarded as non-wild type for species without EUCAST epidemiological cutoff values (ECOFFs). CYP51A sequencing was performed when relevant. Pearson correlation analysis was adopted for comparing activity. Aspergillus accounted for 90% of mold and Candida accounted for 97% of yeast isolates. Thirty (9.3%) Aspergillus fumigatus isolates were classified as resistant, and 10 (3.1%) were classified as non-wild type. Thirteen (4%) were cross-resistant to other mold-active azoles. Target gene alterations were found in 10 (76.9%) isolates, including 4 (30.8%) of environmental origin (TR(34)/L98H [n = 3] and Trip(34)(3)/L98H [n = 1]). Six Aspergillus terreus isolates were resistant, including two (17%) with MICs of >2 mg/liter and M217I alterations. Modal MICs/MIC(50)s (milligrams per liter) against Candida spp. were ≤0.004/≤0.004 for C. albicans and C. dubliniensis, 0.008/0.008 for C. tropicalis, 0.016/0.016 for C. parapsilosis, 0.06/0.06 for C. glabrata, and 0.125/0.125 for C. krusei. A non-wild-type phenotype was observed for 6.6% of isolates (C. glabrata [11.8%] and C. tropicalis [12.3%], specifically). All of these isolates were nonsusceptible/non-wild type to fluconazole (96.1%) or voriconazole (86.2%). Low MICs were found for several other species, except Scedosporium apiospermum and Fusarium. The best correlation was found between isavuconazole and voriconazole overall but for A. terreus and Mucorales to itraconazole and posaconazole, respectively. Isavuconazole displayed broad in vitro activity. Acquired resistance was infrequent except in A. terreus, C. glabrata, and C. tropicalis and, when present, was associated with cross-resistance to other azoles. Revising the EUCAST breakpoints for A. fumigatus (defining an MIC of 2 mg/liter as intermediate [“I”]) would minimize major errors.