OBJECTIVES: Candida auris has emerged as a multidrug-resistant yeast in healthcare settings throughout the world and recently in the United States. The fungus can cause invasive infections associated with high mortality, colonize patients and contacts, and persist on environmental surfaces for months. Whole-genome sequencing (WGS) and phylogenetic analysis of patient isolates from five countries revealed four distinct populations characterized by geography (South Asian, South African, East Asian, and South American clades). We characterized the molecular epidemiology of C. auris in the United States to inform understanding of transmission patterns and outbreak response. 

METHODS: We performed WGS on >300 C. auris isolates obtained from clinical and screening cases identified within ten U.S. states: California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma. Pairwise SNP comparisons of multiple isolates from the same patient and between patients within a facility with active transmission were examined. We sequenced all isolates using Illumina technology (yielding 50-200X coverage) and used a PacBio C. auris reference for comparison. Using the NASP pipeline, we mapped reads using BWA and SAMtools to identify SNPs. We performed principal component analysis using Hamming distance and the adegenet R package. 

RESULTS: We found all four known C. auris populations represented in the United States. Patient isolates from California, Connecticut, Massachusetts, Maryland, New Jersey, New York, and Oklahoma clustered with isolates from India and Pakistan (South Asian clade). Similar results were found for other states. Patient isolates from Florida, Illinois, and Massachusetts clustered with those from Venezuela and Colombia (South American clade). The patient isolate from Indiana resembled those from South Africa, and two people from New York had isolates that resembled those from Japan and South Korea and clustered to the East Asian clade. Five patients had been hospitalized in a country with known C. auris transmission before C. auris identification. Isolates from each of these patients were highly related to isolates from the country of previous hospitalization. Little intra-host genetic diversity of C. auris was observed within each patient (median SNPs 3, range 0-21). Patient isolates within each facility with active transmission had similarly limited diversity (median SNPs 3, range 0-12).

CONCLUSION: WGS has helped public health officials define, track, and monitor C. auris outbreaks in the United States. These findings suggest multiple recent introductions and support heightened monitoring for C. auris in patients recently hospitalized in a country with known transmission. Minimal diversity observed within and between patients in a facility further suggests recent transmission and need for infection control measures.

Using Whole-Genome Sequencing to Identify Recent Introductions and Track the Spread of Candida auris in the United States