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Biological Health Hazard – Invasive, Multi drug-Resistant Candida auris: USA

2016/11/09

CANDIDA AURIS – AMERICAS (02): USA, FIRST ISOLATES
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Published Date: 2016-11-05 11:51:44
Subject: PRO/EDR> Candida auris – Americas (02): USA, 1st isolates
Archive Number: 20161105.4608846

Date: Friday, 4 November 2016
Source: CDC Morbidity and Mortality Weekly Report (MMWR) Early Release [edited]

Investigation of the First 7 Reported Cases of _Candida auris_, a Globally Emerging Invasive, Multidrug-Resistant Fungus — USA, May 2013-August 2016
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_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 1st 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 UK (2-7). To determine whether _C. auris_ is present in the USA 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 1st 7 USA cases of _C. auris_ infection reported to CDC as of 31 Aug 2016. Data from these cases suggest that transmission of _C. auris_ might have occurred in USA 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 3 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 USA, 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 [for Table, see source URL – Mod.LL]) were reported to CDC (1 in 2013, 1 in 2015, and 5 in 2016). 6 of 7 cases were identified through retrospective review of microbiology records from reporting hospitals and reference laboratories. Cases were reported from 4 states: Illinois (n = 2, single hospital), Maryland (n = 1), New Jersey (n = 1), and New York (n = 3, 3 different hospitals). Recent travel outside the USA 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. 5 patients had _C. auris_ initially isolated from blood, 1 from urine, and 1 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 5 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 1 patient had persistently positive _C. auris_ cultures for 10 days, despite having an isolate that was susceptible to the treatment administered. 2 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 31 Aug 2016, 4 of the 7 patients, all of whom had bloodstream infections, died during the weeks to months after the identification of _C. auris_.

In 2 separate circumstances, 2 patients were hospitalized in the same hospital. The 1st instance included the 2 patients from Illinois who were admitted to the same hospital on 3 separate occasions but were on different floors or wings of the hospital. These 2 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 2nd 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. auris_ was identified in the Maryland hospital.

Specimens for surveillance cultures to evaluate patients for colonization were taken from the 3 living patients (1 with _C. auris_ in the blood, 1 in urine and 1 in the external ear canal). In all 3 cases, cultures yielded _C. auris_ from at least 1 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. auris_. _C. auris_ was not detected in this patient’s hospital room after terminal cleaning with sodium hypochlorite solution and ultraviolet light.

5 of 7 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. 5 of 7 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 3 classes of antifungal medications.

Whole-genome sequencing was performed on isolates from 6 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 less than 10 SNPs, which was on same order of magnitude as the 6-SNP differences identified among multiple isolates from specimens obtained over a 10-day period from the Maryland patient. These USA isolates were related to isolates from South Asia (less than 60 SNPs apart). Isolates from the 2 Illinois patients were nearly identical (less than 10 SNPs apart) and were most closely related to isolates from South America (less than 150 SNPs apart). Furthermore, differences of less than or equal to 5 SNPs were identified between the environmental and patient isolates in Illinois. As a point of reference, isolates from different continents are tens of thousands of SNPs apart (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.

Discussion
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_C. auris_ is an emerging cause of Candida infections in the USA. 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 USA. Although transmission to patients in USA 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.

References
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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.
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.
3. Chowdhary A, Sharma C, Duggal S, et al: New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis 2013;19:1670-3.
4. Magobo RE, Corcoran C, Seetharam S, Govender NP. Candida auris-associated candidemia, South Africa. Emerg Infect Dis 2014;20:1250-1.
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.
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.
7. Emara M, Ahmad S, Khan Z, et al. Candida auris candidemia in Kuwait, 2014. Emerg Infect Dis 2015;21:1091-2.
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 20 Oct 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.

[Authors: Vallabhaneni S, Kallen A, Tsay S, et al]

Communicated by:
ProMED-mail
<promed@promedmail.org>

[These are the 1st reported isolates identified in the USA. Echinocandins remain the drugs of choice for this emerging infection which can be difficult to identify in the standard hospital microbiology lab. – Mod.LL

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/promed/p/106.]

See Also

Candida auris – Americas: emerg, drug-resist, nosocom pathogen, PAHO/WHO, alert 20161005.4537152
Candida auris: emerging, drug-resistant, nosocomial pathogen, alert 20160702.4322149
………………………………………….ll/je/dk

Source:
A ProMED-mail post
ProMED-mail is a program of the International Society for Infectious Diseases


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