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.

To understand the epidemiology and susceptibility patterns of yeast infections in Ontario, Canada, we examined 4,715 clinical yeast isolates submitted to our laboratory for antifungal susceptibility testing from 2014 to 2018. Candida 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 to 2018, but the total numbers of yeast isolates sent for testing increased, with an annual 7.4% change. 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%) isolates. Only 1% of C. glabrata isolates 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. There were mutations in the gene for the catalytic subunit of 1,3-beta-glucan synthase-mediated echinocandin resistance in 3 of 3 C. albicans strains, 3 of 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 TAO orthologs in 1 C. tropicalis strain. While antifungal resistance rates remain low among yeast isolates in Ontario, ongoing surveillance is necessary to inform empirical therapy for optimal patient management and to guide antifungal stewardship.