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Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus — United States, May 2013–August 2016 | MMWR

Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus — United States, May 2013–August 2016 | MMWR
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MMWR Weekly
Vol. 65, No. 44
November 11, 2016
 
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Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus — United States, May 2013–August 2016


On November 4, 2016, this report was posted online as an MMWR Early Release.
Snigdha Vallabhaneni, MD1; Alex Kallen, MD2; Sharon Tsay, MD1,3; Nancy Chow, PhD1; Rory Welsh, PhD1; Janna Kerins, VMD3,4; Sarah K. Kemble, MD4; Massimo Pacilli, MS4; Stephanie R. Black, MD4; Emily Landon, MD5; Jessica Ridgway, MD5; Tara N. Palmore, MD6; Adrian Zelzany, PhD6; Eleanor H. Adams, MD7; Monica Quinn, MS7; Sudha Chaturvedi, PhD7; Jane Greenko, MPH7; Rafael Fernandez, MPH7; Karen Southwick, MD7; E. Yoko Furuya, MD8; David P. Calfee, MD9; Camille Hamula, PhD10; Gopi Patel, MD10; Patricia Barrett; MSD11; Patricia Lafaro12; Elizabeth L. Berkow, PhD1; Heather Moulton-Meissner, PhD2; Judith Noble-Wang, PhD2; Ryan P. Fagan, MD2; Brendan R. Jackson, MD1; Shawn R. Lockhart, PhD1; Anastasia P. Litvintseva, PhD1; Tom M. Chiller, MD1 (View author affiliations)
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Summary

What is already known about this topic?
Candida auris is an emerging pathogenic fungus that has been reported from at least a dozen countries on four continents during 2009–2015. The organism is difficult to identify using traditional biochemical methods, some isolates have been found to be resistant to all three major classes of antifungal medications, and C. auris has caused health care–associated outbreaks.
What is added by this report?
This is the first description of C. auriscases in the United States. C. aurisappears to have emerged in the United States only in the last few years, and U.S. isolates are related to isolates from South America and South Asia. Evidence from U.S. case investigations suggests likely transmission of the organism occurred in health care settings.
What are the implications for public health practice?
It is important that U.S. laboratories accurately identify C. auris and for health care facilities to implement recommended infection control practices to prevent the spread of C. auris. Local and state health departments and CDC should be notified of possible cases of C. auris and of isolates of C. haemulonii and Candida spp. that cannot be identified after routine testing.

On November 4, 2016, this report was posted online as an MMWR Early Release.
Snigdha Vallabhaneni, MD1; Alex Kallen, MD2; Sharon Tsay, MD1,3; Nancy Chow, PhD1; Rory Welsh, PhD1; Janna Kerins, VMD3,4; Sarah K. Kemble, MD4; Massimo Pacilli, MS4; Stephanie R. Black, MD4; Emily Landon, MD5; Jessica Ridgway, MD5; Tara N. Palmore, MD6; Adrian Zelzany, PhD6; Eleanor H. Adams, MD7; Monica Quinn, MS7; Sudha Chaturvedi, PhD7; Jane Greenko, MPH7; Rafael Fernandez, MPH7; Karen Southwick, MD7; E. Yoko Furuya, MD8; David P. Calfee, MD9; Camille Hamula, PhD10; Gopi Patel, MD10; Patricia Barrett; MSD11; Patricia Lafaro12; Elizabeth L. Berkow, PhD1; Heather Moulton-Meissner, PhD2; Judith Noble-Wang, PhD2; Ryan P. Fagan, MD2; Brendan R. Jackson, MD1; Shawn R. Lockhart, PhD1; Anastasia P. Litvintseva, PhD1; Tom M. Chiller, MD1 (View author affiliations)
View suggested citation

Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (27). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.
The emergence of C. auris raises several serious concerns for public health. First, many isolates are multidrug-resistant, with some strains having elevated minimum inhibitory concentrations to drugs in all three major classes of antifungal medications (9), a feature not found in other clinically relevant Candida species. Second, C. auris is challenging to identify, requiring specialized methods such as matrix-assisted laser desorption/ionization time-of-flight or molecular identification based on sequencing the D1-D2 region of the 28s ribosomal DNA. When using common biochemical methods such as analytical profile index strips or the VITEK 2, C. auris is often misidentified as other yeasts (most commonly Candida haemulonii, but also Candida famata, Saccharomyces cerevisiae, and Rhodotorula glutinis). Finally, C. auris has caused outbreaks in health care settings (10). Multidrug resistance and health care–associated transmission are often found with resistant bacteria, such as carbapenem-resistant Enterobacteriaceae, but have been uncommon among Candida spp.
To determine whether C. auris cases were occurring in the United States, CDC issued a clinical alert (8) in June 2016, requesting that laboratories report C. auris isolates to state and local health departments and CDC. Given the challenges of C. auris identification, clinical laboratories were encouraged to forward C. haemulonii isolates and isolates not identified beyond Candida spp. by conventional methods to state public health laboratories and CDC for further characterization. A case was defined as confirmed isolation of C. auris in a specimen from a patient at a U.S. health care facility. For all reported cases, patient information and available clinical isolates were obtained for resistance testing and whole-genome sequencing. Among cases in patients who were not deceased, cultures from various patient body sites were obtained to seek evidence of persistent colonization. One patient was hospitalized at the time of the report, allowing for collection of environmental cultures from the hospital room.
Seven C. auris cases occurring during May 2013–August 2016 (Table) were reported to CDC (one in 2013, one in 2015, and five in 2016). Six of seven cases were identified through retrospective review of microbiology records from reporting hospitals and reference laboratories. Cases were reported from four states: Illinois (n = 2, single hospital), Maryland (n = 1), New Jersey (n = 1), and New York (n = 3, three different hospitals). Recent travel outside the United Stated was documented for only one patient: the 2013 New York patient had been transferred less than 1 week earlier from a hospital in the Middle East. Five patients had C. auris initially isolated from blood, one from urine, and one from the external ear canal.
All patients had serious underlying medical conditions, including hematologic malignancies (n = 2), bone marrow transplantation (n = 1), short gut syndrome requiring total parenteral nutrition and corticosteroid use (n = 1), paraplegia with a chronic urinary catheter (n = 1), idiopathic acute respiratory failure requiring high-dose corticosteroids (n = 1), severe peripheral vascular disease and skull base osteomyelitis (n = 1), and brain tumor and recent villous adenoma resection (n = 1). Median time from admission to isolation of C. auris was 18 days (range = 0–231). All five patients with C. auris bloodstream infections had central venous catheters at the time C. auris was identified, and all were treated with echinocandins, a type of antifungal medication; one patient also received liposomal amphotericin B. All patients with bloodstream infections eventually had documented clearance of C. auris from the bloodstream, although one patient had persistently positive C. auris cultures for 10 days, despite having an isolate that was susceptible to the treatment administered. Two patients had recurrent C. auris candidemia episodes 3 and 4 months after the initial episode. C. auris was repeatedly isolated from the urine of a patient with a urinary catheter, even after treatment with fluconazole, to which the isolate was susceptible. The patient with the external ear canal isolate was not treated with an antifungal medication. As of August 31, 2016, four of the seven patients, all of whom had bloodstream infections, died during the weeks to months after the identification of C. auris.
In two separate circumstances, two patients were hospitalized in the same hospital. The first instance included the two patients from Illinois who were admitted to the same hospital on three separate occasions but were on different floors or wings of the hospital. These two patients were subsequently also admitted to a long-term acute care hospital within days of one another, although their admission dates did not overlap. The second instance involved the patients identified in Maryland and New Jersey. The patient identified in Maryland was a resident of New Jersey and had been hospitalized at the same time as the New Jersey patient, in the same New Jersey hospital, but on a different ward. This overlapping admission occurred approximately 6 months before C. auriswas identified in the Maryland hospital.
Specimens for surveillance cultures to evaluate patients for colonization were taken from the three living patients (one with C. auris in the blood, one in urine and one in the external ear canal). In all three cases, cultures yielded C. auris from at least one body site, including groin, axilla, nares, and rectum, 1–3 months after initial detection of C. auris. Environmental cultures of the hospital room were collected during a subsequent hospitalization of one of the Illinois patients who had a C. auris bloodstream infection 3 months earlier, and who remained persistently colonized in multiple body sites; samples taken from the mattress, bedside table, bed rail, chair, and windowsill all yielded C. aurisC. auris was not detected in this patient’s hospital room after terminal cleaning with sodium hypochlorite solution and ultraviolet light.
Five of seven reported isolates were either misidentified initially as C. haemulonii or not identified beyond Candida spp. at the institution’s microbiology laboratory and were later identified as C. auris at a reference laboratory. Five of seven isolates were resistant to fluconazole; one of these isolates was resistant to amphotericin B, and another isolate was resistant to echinocandins. No isolate was resistant to all three classes of antifungal medications.
Whole-genome sequencing was performed on isolates from six patients. Isolates identified in Maryland, New Jersey, and New York were closely related to one another (differing by approximately 70 single nucleotide polymorphisms [SNPs]); the isolates from Maryland and New Jersey (the patients admitted to the same New Jersey hospital) differed by <10 10-day="" 6-snp="" a="" america="" among="" and="" apart="" are="" as="" asia="" between="" closely="" continents="" differences="" different="" environmental="" from="" furthermore="" i="" identical="" identified="" illinois.="" illinois="" in="" isolates="" magnitude="" maryland="" most="" multiple="" nearly="" obtained="" of="" on="" order="" over="" patient.="" patient="" patients="" period="" point="" reference="" related="" same="" snps="" south="" specimens="" tens="" the="" these="" thousands="" to="" two="" u.s.="" was="" were="" which="">9
). None of the patients from which isolates were sequenced, including the patient from the 2013 case in the Middle East, had known travel or other direct links to South Asia or South America.
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Discussion

C. auris is an emerging cause of Candida infections in the United States. Although the cases of C. auris described in this report appear related to isolates from South Asia and South America, available epidemiologic information suggests that most were acquired in the United States. Although transmission to patients in U.S. health care settings has not been definitively documented, several findings suggest that transmission occurred. First, whole-genome sequencing results demonstrate that isolates from patients admitted to the same hospital in New Jersey were nearly identical, as were isolates from patients admitted to the same Illinois hospital. The number of SNPs differentiating isolates from the same hospital is comparable to that detected among the multiple isolates from same patient or patient and the environment. Second, patients were colonized with C. auris on their skin and other body sites weeks to months after their initial infection, which could present opportunities for contamination of the health care environment. Third, C. auris was isolated from samples taken from multiple surfaces in one patient’s health care environment, which further suggests that spread within health care settings is possible. To decrease the risk for transmission, health care personnel in acute care settings should use Standard and Contact Precautions (http://www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf) for patients colonized or infected with C. auris. In nursing homes, providers should consider the level of patient care being provided and the presence of transmission risk factors when deciding on the level of precautions. If such patients are transferred to other health care facilities, receiving facilities should be notified of the presence of this multidrug-resistant organism to ensure appropriate precautions are continued. Facilities should ensure thorough daily and terminal cleaning of rooms of patients with C. auris infections, including use of an EPA-registered disinfectant with a fungal claim. Facilities and laboratories are requested to continue to report cases and forward isolates of C. haemulonii and Candida spp. that are not identified further after using common laboratory identification methods to state or local health authorities and CDC, who can provide consultation about the need for additional interventions to prevent transmission.*
CDC continues to work with domestic and international partners to conduct epidemiologic studies on the emergence of this organism, risk factors for infection, and transmission mechanisms, and to evaluate the effectiveness of current infection control guidance to make additional recommendations.
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Acknowledgments

Melvin Weinstein, Nancy Wengenack, Nathan Wiederhold.
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Corresponding author: Snigdha Vallabhaneni, svallabhaneni@cdc.gov, 404-639-3411.
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1Mycotic Diseases Branch, Division of Food Water and Environmental Diseases, CDC; 2Division of Healthcare Quality Promotion, CDC; 3Epidemic Intelligence Service, Center for Surveillance, Epidemiology and Laboratory Services, CDC; 4Chicago Department of Public Health, Chicago, Illinois; 5University of Chicago, Chicago, Illinois; 6National Institutes of Health Clinical Center, Bethesda, Maryland; 7New York State Department of Health, New York; 8Columbia University College of Physicians & Surgeons, New York, New York; 9Weill Cornell Medicine, New York, New York; 10Mount Sinai Health System/Icahn School of Medicine at Mount Sinai, New York, New York; 11New Jersey Department of Health, Trenton, New Jersey; 12Robert Wood Johnson University Hospital, New Brunswick, New Jersey.
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References

  1. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 2009;53:41–4. CrossRef PubMed
  2. Lee WG, Shin JH, Uh Y, et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol 2011;49:3139–42. CrossRef PubMed
  3. Chowdhary A, Sharma C, Duggal S, et al. New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis 2013;19:1670–3. CrossRef PubMed
  4. Magobo RE, Corcoran C, Seetharam S, Govender NP. Candida auris-associated candidemia, South Africa. Emerg Infect Dis 2014;20:1250–1. CrossRef PubMed
  5. Calvo B, Melo AS, Perozo-Mena A, et al. First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia. J Infect 2016;73:369–74. CrossRefPubMed
  6. Borman AM, Szekely A, Johnson EM. Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species. mSphere 2016;1(4):e00189–16. CrossRef
  7. Emara M, Ahmad S, Khan Z, et al. Candida auris candidemia in Kuwait, 2014. Emerg Infect Dis 2015;21:1091–2. CrossRef PubMed
  8. CDC. Clinical alert to U.S. healthcare facilities—June 2016: global emergence of invasive infections caused by the multidrug-resistant yeast Candida auris. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html
  9. Lockhart SR, Etienne K, Vallabhaneni S, et al. Simultaneous emergence of multidrug resistant Candida auris on three continents confirmed by whole genome sequencing and epidemiological analyses. Clin Infect Dis . E-pub October 20, 2016.
  10. Schelenz S, Hagen F, Rhodes JL, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control 2016;5:35. CrossRef PubMed
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Return to your place in the textTABLECharacteristics of the first seven cases of Candida auris identified in the United States—May 2013–August 2016
PatientIsolation month/ yearStateSite of C. auris isolationUnderlying medical condition(s)Outcome*
1May 2013New YorkBloodRespiratory failure requiring high-dose corticosteroidsDied
2July 2015New JerseyBloodBrain tumor and recent villous adenoma resectionDied
3April 2016MarylandBloodHematologic malignancy and bone marrow transplantDied
4April 2016New YorkBloodHematologic malignancyDied
5May 2016IllinoisBloodShort gut syndrome requiring total parenteral nutrition and high-dose corticosteroid useSurvived
6July 2016IllinoisUrineParaplegia with long-term, indwelling Foley catheterSurvived
7August 2016New YorkEarSevere peripheral vascular disease and skull base osteomyelitisSurvived
* Mortality was not necessarily attributable to C. auris infection.
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Suggested citation for this article: Vallabhaneni S, Kallen A, Tsay S, et al. Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus — United States, May 2013–August 2016. MMWR Morb Mortal Wkly Rep 2016;65:1234–1237. DOI: http://dx.doi.org/10.15585/mmwr.mm6544e1.

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