Epidemiology and Whole Genome Sequence Typing of Globally Emerging, Multidrug-Resistant Candida auris

Abstract

Background. Candida auris is a multidrug-resistant yeast that can cause invasive fungal infections. It was first described in Japan in 2009, and has since been reported in other parts of the world. We established an international collaboration to understand the epidemiology of this emerging pathogen. Methods. We evaluated a convenience sample of C. auris infections from India, Pakistan, South Africa, and Venezuela during 2012–2015. Antifungal susceptibility testing was conducted according to CLSI standards; breakpoints were defined using those from other Candida spp. Whole genome sequencing typing (WGST) was performed. Patient information was obtained using a standardized case report form. Results. Isolates from 54 patients were evaluated (Pakistan 19, India 19, South Africa 10, Venezuela 5, and 1 reference isolate from Japan). All were resistant to fluconazole, 54% to voriconazole, and 7% to echinocandins; resistance to amphotericin B (MIC ≥2) was found in 29% of 21 isolates tested. At least 24% of isolates were resistant to ≥2 antifungal classes. Isolates grouped into distinct South Asian, East Asian, African, and South American clades by WGST. Clades were separated by several thousand single nucleotide polymorphisms (SNPs), but within each clade, isolates were clonal (0–70 SNP differences). Among 38 patients with clinical information, median age was 54 years and 62% were male. Possible risk factors included central venous catheter (CVC) use (78%), surgery in the previous 90 days (50%), recent antifungal therapy (47%), and diabetes (42%). Median time from admission to C. auris culture was 17 days; 63% of patients had bloodstream infections, 16% had urinary tract infections, and 61% died. Conclusion. C. auris is an emerging healthcare-associated pathogen most commonly identified in patients with CVCs and recent surgery and antifungal therapy. It is associated with higher mortality than other Candida spp., and treatment options are limited because of the high prevalence of antifungal resistance. Puzzlingly, WGST analysis suggests emergence at least 4 distinct clades with high genomic similarity within geographical regions. Further exploration of risk factors for infection and transmission mechanisms is needed to inform control measures.