title: Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses.
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.
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia; gyi2@cdc.gov.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Kizee A
authors.initials: KA
authors.lastname: Etienne
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Vallabhaneni
authors.affiliation: Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, and.
authors.forename: Joveria
authors.initials: J
authors.lastname: Farooqi
authors.affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chowdhary
authors.affiliation: National Institute for Communicable Diseases-Centre for Opportunistic, Tropical and Hospital Infections, a Division of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Nelesh P
authors.initials: NP
authors.lastname: Govender
authors.affiliation: Division of Infectious Diseases, Federal University of São Paulo-UNIFESP, Brazil.
authors.forename: Arnaldo Lopes
authors.initials: AL
authors.lastname: Colombo
authors.affiliation: Department of Infectious Diseases, School of Medicine, Universidad del Zulia, Maracaibo, Venezuela.
authors.forename: Belinda
authors.initials: B
authors.lastname: Calvo
authors.affiliation: Broad Institute, MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Cuomo
authors.affiliation: Broad Institute, MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desjardins
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Berkow
authors.affiliation: JMI Laboratories, North Liberty, Iowa.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: National Institute for Communicable Diseases-Centre for Opportunistic, Tropical and Hospital Infections, a Division of the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Rindidzani E
authors.initials: RE
authors.lastname: Magobo
authors.affiliation: Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, and.
authors.forename: Kauser
authors.initials: K
authors.lastname: Jabeen
authors.affiliation: Centers for Disease Control and Prevention Field Epidemiology and Laboratory Training Program, Islamabad, Pakistan.
authors.forename: Rana J
authors.initials: RJ
authors.lastname: Asghar
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, and.|Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Brendan
authors.initials: B
authors.lastname: Jackson
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Tom
authors.initials: T
authors.lastname: Chiller
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Litvintseva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D058387:Candidemia / Q000453:epidemiology / Q000382:microbiology; D002177:Candidiasis / Q000453:epidemiology* / Q000209:etiology / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D021903:DNA, Ribosomal Spacer; D025141:Drug Resistance, Fungal; D018432:Drug Resistance, Multiple; D005260:Female; D016681:Genome, Fungal; D014943:Global Health; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D000073336:Whole Genome Sequencing; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D021903:DNA, Ribosomal Spacer; D012339:RNA, Ribosomal, 28S; D003577:Cytochrome P-450 Enzyme System
keywords: 
  Candida auris
  ; amphotericin B resistance; candidemia; fluconazole resistance; whole genome sequence typing.