The activity of 7 antifungal agents was evaluated against 3,557 invasive yeasts and moulds collected in 29 countries worldwide during 2014-2015. Epidemiological cutoff values (ECVs) published in the CLSI M59 document were applied for species with no clinical breakpoints. Echinocandin susceptibility rates were 95.9% to 100.0% for the 5 most common Candida species except anidulafungin and C. parapsilosis (88.7% susceptible/100.0% wild-type). Fluconazole resistance ranged from 8.0% for C. glabrata to 0.4% for C. albicans. Seven Candida species displayed 100.0% wild-type amphotericin B and C. dubliniensis and C. lusitaniae exhibited wild-type echinocandin MIC results. The highest fluconazole, voriconazole, and posaconazole MIC values for Cryptococcus neoformans var. grubii were 8 μg/mL, 0.12 μg/mL, and 0.25 μg/mL, respectively. A. fumigatus were 100.0% wild-type for caspofungin and amphotericin B, but 3 (0.8%) of these isolates were non- wild-type to itraconazole (2 isolates) or voriconazole (1 isolate). Mutations on FKS hotspots (HS) were detected among 13/20 Candida isolates (16/20 were C. glabrata) displaying echinocandin MIC>ECV. Most isolates carrying FKS HS mutations were resistant to 2 or more echinocandins. Five fluconazole-nonsusceptible C. albicans were submitted to whole genome sequencing analysis. Gain of function, Erg11 heterozygous, and Erg3 homozygous mutations were observed in 1 isolate each. One isolate displayed MDR1 promoter allele alterations associated with azole resistance. Elevated expression of MDR1 or CDR2 was observed among 3 and 1 isolates, respectively. Echinocandin and azole resistance is still uncommon among contemporary fungal isolates; however, resistance mechanisms to antifungals were observed among Candida spp. showing that resistance can emerge and monitoring is warranted.
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