Genomic Tracking of Candida auris Novel Resistance Markers in Hospital-Acquired Infections Across Urban ICUs

Background: Candida auris, a multidrug-resistant fungal pathogen, poses a significant threat in urban Indian intensive care units (ICUs) due to its high transmissibility and resistance to antifungals. This study investigates the genomic epidemiology and novel resistance markers of C. auris in hospital-acquired infections across urban Indian hospitals.Methods: From January 2023 to September 2025, 184 C. auris isolates were collected from 172 patients in six tertiary care ICUs. Clinical samples (blood, urine, respiratory, wound) and environmental swabs were analyzed. Isolates were identified via MALDI-TOF MS and ITS1-5.8S-ITS2 PCR. Antifungal susceptibility testing followed CLSI M27-A3 guidelines for fluconazole, voriconazole, micafungin, amphotericin B, and flucytosine. Whole-genome sequencing (WGS) was performed using Illumina NextSeq 2000, with variants identified via ResFinder 4.3.0. Phylogenetic and transmission analyses used IQ-TREE and TransPhylo. Statistical associations were assessed with chi-square, Fisher’s exact, and Poisson regression tests (p<0.05). Results: Out of 184 isolates, 66.3% were from bloodstream infections. Incidence rose from 1.8 to 4.2 cases per 10,000 ICU-days (p<0.001). Resistance rates were 92.4% (fluconazole), 75.0% (voriconazole), 34.8% (micafungin), 15.2% (amphotericin B), and 7.6% (flucytosine); 14.1% were pan-resistant. WGS identified Clade I (64.1%), Clade IV (29.3%), and Clade III (6.5%), with novel markers: TAC1B p.Arg673fs (28.3%, OR: 5.1 for fluconazole resistance, p<0.001), ERG11 g.-245A>G (20.7%), and FKS1 p.Ser645Pro (13.0%). Nosocomial transmission accounted for 68% of cases, with Clade I showing higher transmissibility (R0=1.8). Environmental positivity was 33.9%. Mortality was 38.4%, highest in pan-resistant cases (OR: 2.9, p=0.008).Conclusion: C. auris in urban Indian ICUs exhibits escalating resistance and transmission, driven by novel genomic markers. Routine WGS and enhanced infection control are critical to mitigate this public health threat.