Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses

By S. Lockhart, Kizee A. Etienne, S. Vallabhaneni, J. Farooqi, A. Chowdhary, N. Govender, A. Colombo, B. Calvo, Christina A. Cuomo, C. Desjardins and 9 more. Clinical Infectious Diseases, 2017

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Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Subfields: Epidemiology, Infectious Diseases, Ophthalmology

View Paper: https://www.semanticscholar.org/paper/c8d8e54651d8fb7a7ece68270cd2630d1cd0df39

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Citations in the corpus

Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016 (2019, background): “S90 • OFID 2019:6 (Suppl 1) • Pfaller et al SENTRY Program Candida Surveillance (1997–2016) • OFID 2019:6 (Suppl 1) • S91 [93, 94], and emerging resistance mechanisms [20, 68] highlight the importance of local and global surveillance studies.”
Resistance of Candida to azoles and echinocandins worldwide. (2019, background): “auris, as well as other Candida species, from environmental surfaces and reusable equipment in healthcare facilities, implying that contaminated surfaces may be the source of transmission [45,53].”
First hospital outbreak of the globally emerging Candida auris in a European hospital (2016, background): “auris isolates in the same geographic areas [14, 15].”
Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment (2017, background): “Prevention strategies to limit development of MDR and XDR infections are critical.”