Antifungal susceptibility of clinical yeast isolates from a large Canadian reference laboratory and application of whole genome sequence analysis to elucidate mechanisms of acquired resistance.

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Antifungal susceptibility of clinical yeast isolates from a large Canadian reference laboratory and application of whole genome sequence analysis to elucidate mechanisms of acquired resistance.

Antimicrob Agents Chemother. 2020 Jun 22;:

Authors: McTaggart LR, Cabrera A, Cronin K, Kus JV

Abstract
To understand the epidemiology and susceptibility patterns of yeast infections in Ontario, we examined 4715 clinical yeast isolates submitted to our laboratory for antifungal susceptibility testing from 2014-2018. C. albicans was the most frequently submitted species (43.0%) followed by C. glabrata (21.1%), C. parapsilosis (15.0%), and C. tropicalis (6.2%). Twenty-three other Candida spp. (11.6%) and 4 non-Candida species (3.1%) were also identified. Few changes in species distribution were observed from 2014-2018, but the total number of yeast isolates sent for testing increased with an annual percent change of 7.4%. According to CLSI clinical breakpoints, resistance rates remained low overall. Moderate fluconazole resistance was noted among C. glabrata (9%), C. parapsilosis (9%), and C. tropicalis (12%). Only 1% of C. glabrata were resistant to caspofungin, micafungin, and anidulafungin. Whole genome sequence analysis confirmed 11 cases of acquired resistance to azoles or echinocandins via in-host evolution. Mutations in the gene for the catalytic subunit of 1,3-beta-glucan synthase mediated echinocandin resistance in 3/3 C. albicans strains, 3/4 C. glabrata strains, and 1 strain of C. tropicalis Azole resistance was likely caused by a homozygous ERG3 mutation in 1 C. albicans strain and a previously undescribed chromosomal duplication event involving ERG11 and TAC1 orthologs in 1 C. tropicalis strains. While antifungal resistance rates remain low among yeast isolates in Ontario, ongoing surveillance is necessary to inform empiric therapy for optimal patient management and to guide antifungal stewardship.

PMID: 32571812 [PubMed - as supplied by publisher]