Shawn R Lockhart1, Kizee A Etienne2, Snigdha Vallabhaneni2, Joveria Farooqi3, Anuradha Chowdhary4, Nelesh P Govender5, Arnaldo Lopes Colombo6, Belinda Calvo7, Christina A Cuomo8, Christopher A Desjardins8, Elizabeth L Berkow2, Mariana Castanheira9, Rindidzani E Magobo5, Kauser Jabeen3, Rana J Asghar10, Jacques F Meis11,12, Brendan Jackson2, Tom Chiller2, Anastasia P Litvintseva2. 1. Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia; gyi2@cdc.gov. 2. Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. 3. Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, and. 4. Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, India. 5. National Institute for Communicable Diseases-Centre for Opportunistic, Tropical and Hospital Infections, a Division of the National Health Laboratory Service, Johannesburg, South Africa. 6. Division of Infectious Diseases, Federal University of São Paulo-UNIFESP, Brazil. 7. Department of Infectious Diseases, School of Medicine, Universidad del Zulia, Maracaibo, Venezuela. 8. Broad Institute, MIT and Harvard, Cambridge, Massachusetts. 9. JMI Laboratories, North Liberty, Iowa. 10. Centers for Disease Control and Prevention Field Epidemiology and Laboratory Training Program, Islamabad, Pakistan. 11. Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, and. 12. Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
Abstract
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. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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