Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris

• Published in: Antimicrobial agents and chemotherapy 2019-01, Vol.63 (1)
• Main Authors: Hou, Xin, Lee, Annie, Jiménez-Ortigosa, Cristina, Kordalewska, Milena, Perlin, David S, Zhao, Yanan
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Anidulafungin - pharmacology; Antifungal Agents; Antifungal Agents - pharmacology; Candida; Candida - drug effects; Candida - enzymology; Candida - genetics; Candida - isolation & purification; Candidiasis - drug therapy; Candidiasis - microbiology; Caspofungin - pharmacology; Cytochrome P-450 Enzyme System; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; DNA Mutational Analysis; Drug Resistance, Fungal; Drug Resistance, Fungal - genetics; Fluconazole - pharmacology; Fungal Proteins; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression; Glucosyltransferases; Glucosyltransferases - genetics; Glucosyltransferases - metabolism; Humans; Mechanisms of Resistance; Micafungin - pharmacology; Mutation; Nucleic Acid Denaturation; Polymerase Chain Reaction; Polymerase Chain Reaction - methods; Voriconazole - pharmacology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01811-18

is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of mutations conferring azole resistance and mutations associated with echinocandin resistance in Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex assay and a simplex HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in ; S639F in HS1) within 2 h. Assays were validated by testing a panel of 94 clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing susceptibility-based assays to identify azole- and/or echinocandin-resistant , and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively.