Investigation of suspected Candidozyma auris outbreaks in Malaysia using integrated genomic, clinical, and antifungal susceptibility analyses

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungus with limited genomic epidemiological data from Malaysia. This study investigated the genomic epidemiology, clinical characteristics and antifungal susceptibility of C. auris outbreak isolates using an integrated whole-genome sequencing (WGS) approach. Eleven clinical C. auris isolates from five healthcare facilities across three Malaysian states were analysed alongside clinical and epidemiological data. Antifungal susceptibility testing was performed for azoles, echinocandins, amphotericin B, flucytosine, and manogepix. Among 11 patients, seven had candidemia and four were colonized. Median age was 48 years, with diabetes mellitus, chronic kidney disease, and hypertension as the most common comorbidities. All candidemia patients had urinary and central venous catheters; 71% required mechanical ventilation, 43% had haemodialysis and recent surgery, respectively. Recent antibiotic exposure was common, whereas none had prior antifungal therapy. All isolates belonged to Clade I but separated into distinct genomic clusters, supporting healthcare-associated transmission within clusters and simultaneous circulation of multiple genomic groups. All Johor-associated isolates were fluconazole resistant and carried ERG11 K143R and CDR1 V704L substitutions. An ERG5 variant was detected in non-Johor isolates with amphotericin B minimum inhibitory concentrations (MICs) ≥ 1 µg/ml. The MICs for other antifungals remained low across isolates. Echinocandin therapy was initiated in 27% of patients, with one survivor. Our C. auris showed genomic diversity, distinct healthcare-associated clustering, and variable antifungal susceptibility. Integrating WGS with clinical and susceptibility data enhanced outbreak investigation of C. auris.