Emergence ofCandida auris: An International Call to Arms

On June 24, 2016, the Centers for Disease Control and Prevention (CDC) issued an extraordinary alert, advising US healthcare facilities “to be on the lookout for Candida auris in patients” [1]. The alert noted that C. auris infections had been identified in several countries since 2009. Although cases have not been described in the United States, CDC reported that a C. auris isolate from 2013 was detected during ongoing surveillance. Within a week, Public Health England (PHE) announced that C. auris was recovered from healthcare facilities in that country, and 1 hospital has been managing an outbreak involving more than 40 patients in an intensive care unit (ICU) since April 2015 [2]. The outbreak persisted despite regular patient screening, environmental decontamination, ward closure, and other enhanced infection control interventions [2]. In this issue of Clinical Infectious Diseases, Lockhart and colleagues describe the study that prompted the CDC alert [3]. Reports of C. auris infections have been published from Japan, South Korea, India, South Africa, Kuwait, and Venezuela, describing 45 patients with candidemia and 26 patients with other invasive diseases or colonization [4–11]. The earliest case to date was identified in retrospect by DNA sequencing of a Korean bloodstream isolate from 1996 [6]. These studies established salient features of C. auris invasive infections. Candida auris is typically misidentified by commercial API-20C or Vitek-2 systems (Table 1). Infections often occur as part of nosocomial outbreaks. Patients range from neonates to the elderly and have well-recognized risk factors for invasive candidiasis. A large majority of isolates are fluconazole resistant, and amphotericin B and echinocandin resistance rates are approximately 30%–40% and approximately 5%–10%, respectively. Almost half of isolates are multidrug resistant (MDR; resistant to 2 or more antifungal classes), and a small percentage is pandrug resistant. Optimal treatment regimens are unknown. Mortality rates are high, approaching 70% during candidemia. CDC investigators were aware of these data when they determined that an outbreak of yeast infections at a hospital in Pakistan in 2015 was caused by C. auris, rather than Saccharomyces cerevisiae as initially believed. As detailed by Lockhart et al, CDC assembled an international consortium to describe the epidemiology of C. auris infections and compare whole genome sequences of C. auris isolates. The investigative team collected isolates from 54 patients in 18 Pakistani, Indian, South African, and Venezuelan hospitals, and they collected clinical data from 41 patients. Epidemiologic, microbiologic, and clinical findings from this study corroborate those of previously published reports, as summarized above [4–11]. Three results provide important new insights. First, phylogenetic analysis of whole genome sequences revealed 4 distinct C. auris clades, which were comprised exclusively of isolates from Pakistan–India, South Africa, Venezuela, or Japan (the 2009 type specimen). Almost all isolates within a given phylogeographic clade were highly clonal, differing by fewer than 70 genomewide single nucleotide polymorphisms. Second, specific ERG11 azole–resistance mutations were shared by isolates within clades. Third, a query of >15 000 Candida isolates deposited in the worldwide SENTRY repository since 2004 uncovered only 4 misidentified C. auris from 2009, 2013, 2014, and 2015. The authors reasonably conclude that antifungalresistant C. auris is likely to have emerged recently, independently and almost simultaneously on 3 continents, rather than as a result of worldwide dissemination of a dominant clone. However, the data also indicate that clonal isolates are distributed over large distances within countries and continents. The evidence for hospital outbreaks and clonal spread suggests that C. auris infections may differ from invasive candidiasis due to most other Candida species, which is usually sporadic and caused by genetically distinct, endogenous isolates that are colonizing the patient’s gastrointestinal tract, mucosal surfaces, or skin [13]. E D I T O R I A L C O M M E N TA R Y