EUCAST susceptibility testing of isavuconazole: MIC data for contemporary clinical mould and yeast isolates.

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EUCAST susceptibility testing of isavuconazole: MIC data for contemporary clinical mould and yeast isolates.

Antimicrob Agents Chemother. 2019 Mar 25;:

Authors: Jørgensen KM, Astvad KMT, Hare RK, Arendrup MC

Abstract
Isavuconazole is the newest medical azole. We investigated EUCAST MICs for isavuconazole and seven comparators against 1498 contemporary isolates (2016-2017).EUCAST susceptibility testing was performed. Isavuconazole MIC>2 dilution-steps above the modal MIC were regarded non-wild-type for species without EUCAST ECOFFs. CYP51A sequencing was performed when relevant. Pearson correlation analysis was adopted for comparing activity.Aspergillus accounted for 90% of mould and Candida for 97% of yeast isolates. Thirty (9.3%) A. fumigatus were classified as resistant and 10 (3.1%) as non-wild-type. Thirteen (4%) were cross-resistant to other mould active azoles. Target gene alterations were found in 10 (76.9%), including four (30.8%) of environmental origin (TR34/L98H (n=3), Trip34 3/L98H (n=1)). Six A. terreus were resistant including two (17%) with MIC>2(mg/L and M217I alterations. Modal MIC/MIC50s (mg/L) against Candida spp. were: C. albicans and C. dubliniensis: ≤0.004/≤0.004, C. tropicalis 0.008/0.008, C. parapsilosis 0.016/0.016, C. glabrata 0.06/0.06 and C. krusei 0.125/0.125. Non-wild-type phenotype was observed for 6.6% isolates (C. glabrata 11.8% and C. tropicalis 12.3%, specifically). All of these were non-susceptible/none-wild-type to fluconazole (96.1%) or voriconazole (86.2%). Low MICs were found for several other species except S. apiospermum and Fusarium 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, associated with cross-resistance to other azoles. Revising the EUCAST breakpoints for A. fumigatus (defining MIC=2 mg/L as "I") would minimise major errors.

PMID: 30910898 [PubMed - as supplied by publisher]