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

Clin Infect Dis. 2017 Jan 15;64(2):134-140. doi: 10.1093/cid/ciw691. Epub 2016 Oct 20.

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.

Keywords: Candida auris; amphotericin B resistance; candidemia; fluconazole resistance; whole genome sequence typing..

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antifungal Agents / pharmacology*
  • Candida / classification
  • Candida / drug effects*
  • Candida / genetics*
  • Candida / isolation & purification
  • Candidemia / epidemiology
  • Candidemia / microbiology
  • Candidiasis / epidemiology*
  • Candidiasis / etiology
  • Candidiasis / microbiology*
  • Child
  • Child, Preschool
  • Cytochrome P-450 Enzyme System / genetics
  • DNA, Ribosomal Spacer
  • Drug Resistance, Fungal*
  • Drug Resistance, Multiple*
  • Female
  • Genome, Fungal
  • Global Health
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • RNA, Ribosomal, 28S / genetics
  • Whole Genome Sequencing
  • Young Adult

Substances

  • Antifungal Agents
  • DNA, Ribosomal Spacer
  • RNA, Ribosomal, 28S
  • Cytochrome P-450 Enzyme System