Clade-dependent antifungal resistance and susceptibility in Candidozyma auris: A global scoping review.

BACKGROUND

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungal pathogen that has spread globally since its first identification in 2009 and is now classified as a critical-priority pathogen by the World Health Organization. Distinct genetic clades are associated with variations in geographic distribution, antifungal susceptibility, and resistance mechanisms; however, clade-specific evidence remains fragmented.

AIMS: To systematically map global evidence on clade diversity, antifungal susceptibility patterns, resistance mechanisms, and clinical implications of C. auris.

METHODS

A scoping review was conducted following PRISMA-ScR guidelines. Peer-reviewed primary studies published between 2009 and September 2025 were included if they reported clade attribution and antifungal susceptibility or resistance data. PubMed/MEDLINE, Scopus, and Web of Science were searched. Two reviewers independently screened studies and extracted data using a standardized form.

RESULTS

Of 2050 records identified, 105 studies met inclusion criteria, representing 29 countries and diverse study designs. Whole-genome sequencing was the most common typing method. Antifungal susceptibility varied substantially across clades. High fluconazole resistance was consistently reported (MIC 4 to >256μg/mL). Echinocandins generally retained activity, although reduced susceptibility associated with FKS1 mutations was observed. Resistance mechanisms primarily involved mutations in ERG11, FKS1, and efflux-related genes. Studies also reported challenges in healthcare-associated transmission, environmental persistence, and diagnostic misidentification.

CONCLUSIONS

C. auris exhibits marked clade-dependent variability in antifungal susceptibility and resistance mechanisms. These findings support the need for clade-informed interpretation of susceptibility data, standardized surveillance, improved diagnostics, and development of novel antifungal therapies.