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Candida auris: A Review of Recommendations for Detection and Control in Healthcare Settings

1. Introduction

Candida auris is an emerging multidrug-resistant fungus that has caused outbreaks of invasive infections in healthcare facilities around the world. C. auris has been reported from dozens of countries from six continents and has caused outbreaks in places such as Colombia, India, South Africa, Spain, and the United States ( Healthcare facilities have reported C. auris outbreaks in critically ill hospitalized patients with high crude mortality rates (30% to 72%). Risk factors for C. auris bloodstream infections (BSIs) are similar to the risk factors for other Candida species BSIs, including recent major surgical procedures, diabetes, use of broad-spectrum antibiotics, long-term hospitalizations, and the presence of devices, including breathing tubes, feeding tubes, and central venous catheters. Risk factors for candidemia differ by the population affected. For example, in the United States, patients with neurologic diseases in long-term care with many devices may be at higher risk of developing invasive C. auris infections. Infections can occur in patients of all ages, but most infections have been reported in adults. The ability to accurately identify C. auris and the capacity to implement infection control practices, including environmental cleaning, are critical to control and prevention of C. auris outbreaks. Here we review recommendations for detection and control of C. auris based on published literature and experiences of staff of the U.S. Centers for Disease Control and Prevention (CDC).

2. Candida auris Identification

Identification of C. auris isolates can be challenging, as conventional phenotypic methods for yeast identification may misidentify C. auris isolates as Candida haemulonii, Candida sake, Rhodotorula glutinis, or other Candida species, in part because C. auris is not in the databases or result options for some methods. Based on the CDC’s recommendations for the identification of C. auris, Table 1 describes the most common misidentifications based on frequently used yeast identification methods. However, efforts to improve C. auris identification methods have made substantial progress in the last few years. The development of a high-salt, high-temperature enrichment culture-based method has made it possible to reliably isolate C. auris from complex sample types. Once an isolate is obtained, identification of C. auris can be efficiently accomplished with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. For MALDI-TOF identification, it is important to ensure C. auris is in the reference database. The Bruker Biotyper (Bruker Daltonik GmbH, Bremen, Germany) and the VITEK MS (bioMérieux, Marcy, L’Etoile, France) include C. auris in their Research Use Only and certain versions of their FDA-approved system databases. If MALDI-TOF is not available, laboratories can reliably identify an isolate by sequencing the D1–D2 region of the 28s rDNA or the internal transcribed spacer (ITS) regions of rDNA.

For phenotypic yeast identification, the VITEK 2 system (bioMérieux, Marcy, L’Etoile, France) included C. auris in its recent software upgrade (version 8.01). Recently, a study showed this software update had limited ability to correctly identify C. auris from the African and East Asian clades but was able to accurately identify isolates from the South American clade. Clinical validation of this VITEK 2 system upgrade is pending. Hence, all isolates identified using this system, as C. auris, C. famata, and species in the C. haemulonii complex should be confirmed by MALDI-TOF or DNA sequencing. Validation of the VITEK 2 system would make C. auris isolate identification more accessible, as it is widely used in laboratories.

Beyond improved methods to identify a cultured isolate, a number of culture-independent methods for the detection of C. auris have been recently described. Culture-independent methods are highly attractive because results can be obtained in hours rather than days, allowing for more rapid identification of colonized patients. At the time of writing, clinical evaluations of three culture-independent tests using culture-based gold standards have been published. These include a Taqman quantitative PCR (qPCR), a SYBR green qPCR, and a T2 Magnetic Resonance assay; all performed well with clinical sensitivities and specificities close to or exceeding 90%. In the United States, the Taqman-based qPCR is currently the mostly widely used culture-independent test and is employed for C. auris surveillance at CDC and the Wadsworth Center in New York, as well as an increasing number of Antibiotic Resistance Laboratory Network (AR Lab Network) laboratories. Recent publications have described successes adapting the Taqman qPCR to the BD Max system (Becton Dickinson, NJ, USA), which automates the test and substantially reduces associated labor. Additional promising culture-independent tests have been developed, although their performance with clinical samples is not yet known.

All confirmed identifications of C. auris should be reported to local or national public health authorities, and infection control practices to prevent transmission, should be implemented at facilities where the patients reside.

3. Candida auris Antifungal Susceptibility Testing

Antifungal resistance of C. auris isolates varies across the phylogenetic clades, but multidrug-resistance is common, especially among isolates of the South Asia clade. Susceptibility testing using broth microdilution for azoles and echinocandins or gradient diffusion for azoles, echinocandins, and amphotericin B are preferred. Erroneous susceptibility results have been reported for C. auris using the VITEK 2 for amphotericin B. There are currently no established minimum inhibitory concentration (MIC) breakpoints for susceptibility of C. auris isolates. CDC suggests the following tentative breakpoints based on the breakpoints of closely related Candida species and on expert opinion: fluconazole ≥32 µg/mL, amphotericin B ≥2 µg/mL (round to 2 if an MIC of 1.5 is found using Etest), caspofungin ≥2 µg/mL, micafungin ≥4 µg/mL, and anidulafungin ≥4 µg/mL.

4. Infection Control Practices

Implementation of infection control practices is crucial for controlling C. auris outbreaks in healthcare settings. Lapses in infection control, delays in recognition of cases or delays in the implementation of infection control activities may result in rapid transmission of C. auris among patients. Some Candida are considered commensal organisms common in human flora, and the source of infection is generally autoinoculation, as opposed to patient-to-patient transmission. However, C. auris is highly transmissible among patients, perhaps due to its proclivity for persistent skin colonization. Preliminary data suggest that patients who underwent placement of invasive medical devices or procedures, such as central venous catheters, were at greater risk of C. auris bloodstream infection compared with patients with bloodstream infections caused by other Candida species. Because C. auris commonly colonizes skin, catheters may provide a means for this fungus to enter the bloodstream. The transmissibility of C. auris is likely also driven by its ability to contaminate the patient care environment. C. auris has been found on healthcare surfaces and medical equipment and can persist on such surfaces for long periods. Preventing spread of C. auris is dependent on two elements: 1) identification of cases; and 2) implementation of infection control precautions for all identified cases to minimize likelihood of transmission to other patients. For infection control purposes, a case is considered an occurrence of either C. auris colonization or infection in a patient. The following recommendations for infection control are summarized in Table 2.

Identification of cases: C. auris is transmissible whether a patient has C. auris infection or colonization. Thus, infection control precautions are the same for patients with C. auris infection or colonization. Implementation of these practices starts with the identification of cases. The most basic type of case recognition is the identification of incident clinical cases, meaning C. auris through processing of routine clinical specimens. Candida isolates obtained from a sterile body site should be identified to the species level. Additionally, CDC advises identifying Candida isolates recovered from non-sterile body sites to the species level when: Clinically indicated.C. auris has been detected in the facility or unit.A patient has had an overnight stay in a healthcare facility outside the United States in the preceding year, especially if that stay was in a country with documented C. auris transmission.

The presence of C. auris in any body site can represent a source for transmission and should trigger the implementation of infection control precautions.

Patients with C. auris colonization may also be identified through targeted screening. Screening may be considered when a patient is a close healthcare contact of someone with C. auris infection or colonization, or when a patient has had an overnight healthcare facility stay in a country outside the United States in the preceding year, especially if that country has documented C. auris cases. Screening of patients with overseas healthcare exposure for C. auris is strongly encouraged when the patient has an infection or colonization with carbapenemase-producing Gram-negative bacteria. Point prevalence screenings, in which every patient on a unit or floor is screened at the same time, may be employed to detect unidentified colonized patients if there is evidence or suspicion of transmission in the facility. Screening for C. auris is commonly done using a composite swab of the patient’s axilla and groin regions, as these sites have been determined to be high-yielding. Other body sites or specimens from which C. auris has been isolated include the nose, mouth, external ear canals, urine, wounds, and rectum. The axilla and groin appear to be consistent sites of colonization, although further evaluation is needed.

Hand hygiene: Healthcare personnel (HCP) should practice proper and frequent hand hygiene with alcohol-based hand sanitizer (ABHS) or soap and water. ABHS is effective against C. auris and is preferred for hand hygiene unless the hands are visibly soiled, in which cases handwashing with soap and water is recommended.

Care should be taken to ensure that enough quantities of ABHS, soap, towels, and uncluttered sinks are available in order to facilitate hand hygiene. HCP should be trained on appropriate hand hygiene techniques when hired and retrained at regular intervals. It is important to monitor HCP adherence with recommended hand hygiene practices and provide personnel with feedback regarding their performance.

Transmission-based precautions: All patients in acute care hospitals and long-term care hospitals who are infected or colonized with C. auris should be placed on contact precautions, which includes placing the patient in a single room and using appropriate personal protective equipment (PPE) and restricting patients to their room except for medically necessary procedures. Whenever possible, patients with C. auris infection or colonization should be housed in a single-patient room. If a limited number of single rooms are available, they should be reserved for patients at highest risk for transmission, such as those with uncontained secretions or diarrhea. Patients colonized or infected with C. auris could also be cohorted in a room with other C. auris patients. Cohorting can be challenging as C. auris patients are often co-colonized with other different multidrug-resistant organisms. This has made cohorting impractical in many settings (Table 2).

Nursing homes may consider using less restrictive precautions if the patient’s unit is not experiencing ongoing transmission and if the resident does not have uncontained secretions or excretions. Enhanced barrier precautions have been recommended in these situations by CDC. As part of enhanced barrier precautions, PPE is used when body fluid exposure is anticipated as well as for high contact activities, such as dressing, device care, and changing linens, but is not required for other resident care activities. Under enhanced barrier precautions, residents are not restricted to their rooms and can participate in group activities.

In all settings, transmission-based precautions should be continued for as long as a patient is colonized with C. auris. The typical duration of C. auris colonization remains unknown, although it appears to be protracted while patients are in healthcare settings, and methods for decolonization are not yet established. Therefore, the most conservative strategy is to keep patients with C. auris infection or colonization on transmission-based precautions for the duration of their healthcare facility stays (present and future). To indicate that the patient is on transmission-based precautions and explain what PPE is needed, clear signage should be placed outside the patient’s room.

Environmental cleaning and disinfection: Extensive contamination of the healthcare environment has been described in facilities with C. auris outbreaks, emphasizing the importance of environmental cleaning and disinfection. Environmental services staff should safely remove and clean visible organic material (e.g., bodily fluids, dirt) from patient care area before disinfection. Although quaternary ammonium compounds (QACs) are among the most commonly used disinfectants in healthcare settings, early studies found some of these compounds are ineffective against C. auris. However, interpreting these studies is complicated because diverse methodologies have been utilized. In response, the Environmental Protection Agency (EPA) took two measures to improve disinfectant guidance for C. auris. First, CDC and EPA collaboratively implemented interim guidance for C. auris disinfection using EPA-registered hospital-grade disinfectants known to be effective against Clostridioides difficile spores until further data were available on efficacy of disinfectants against C. auris. Simultaneously, the EPA developed and released SOP-MB-35-00, a standardized quantitative disk carrier method that can be used to evaluate disinfectant efficacy against C. auris.

Disinfectants that meet the 5 log10 reduction performance standard defined by the EPA can acquire a formal C. auris master label kill claim. Recently the EPA has approved the addition of a C. auris claim to the master label of Oxivir 1 (applies to ready to use cleaners and wipes, EPA registration 70627-74 and 70627-77, respectively), a hydrogen peroxide based cleaner; and the Micro-Kill bleach germicidal bleach wipes (EPA registration 37549-1), a product based on sodium hypochlorite. Additionally, the EPA has also approved a request made by CDC regarding a Section 18 emergency exemption (under the Federal Insecticide, Fungicide, and Rodenticide Act), which temporarily permits off-label use of seven additional disinfectants to control C. auris. This action is supported by efficacy data generated at CDC (personal communication D.J. Sexton, CDC) and expands the options available for healthcare facilities working to control C. auris. These developments represent helpful steps in expanding the number of disinfectants available for control of C. auris; however, further disinfectant testing and submissions for formal C. auris claims from the EPA are still needed.

Work at CDC and in related publications by other groups have reaffirmed early concerns that some QAC-based products are not effective, but also indicated the promise of additional QAC chemistries that include alcohol-based products. Thorough daily cleaning and disinfection, with special attention to high-touch surfaces such as bedrails and bedside tables, are needed in patient care areas housing patients on contact precautions for C. auris. Terminal cleaning and disinfection should be performed when the patient is moved from the care area permanently. Chemical fogging, vaporized hydrogen peroxide, ozone, chlorine dioxide, and ultraviolet light, ionization, and titanium dioxide/ultraviolet light, might allow thorough disinfection of difficult-to-reach places, though further evaluations of these methods against C. auris are needed.

It is important to closely monitor adherence to environmental cleaning protocols, including protocols for cleaning solution preparation, contact times, designation of staff members’ assigned areas and objects to clean, and daily and terminal cleaning techniques. Routine environmental testing for C. auris is not recommended. Cultures are costly and time-intensive, and previous investigations have shown that C. auris will generally be detected in the environment where C. auris cases have been found. Some facilities use machines for detection of adenosine triphosphate (ATP) to audit cleaning (not pathogen-specific testing), and standard environmental cleaning audits, such as direct observation or the use of florescent markings, to determine whether surfaces have been cleaned.

5. Treatment and Management of Infections and Colonization

It is highly recommended that C. auris infections be managed in consultation with an infectious disease specialist. Echinocandin drugs are recommended as initial therapy for treatment of C. auris infections, as C. auris isolates are often susceptible to echinocandins but are frequently resistant to the other two main antifungal drug classes (azoles and polyenes). Antifungal treatment management of C. auris infection is similar to other Candida species infections. More details on patients’ treatment and management are summarized in the Infectious Diseases Society of America (IDSA), Clinical Practice Guideline for the Management of Candidiasis published in 2016.

No conclusive evidence exists regarding the effectiveness of protocols for the decolonization of patients with C. auris. During an outbreak of C. auris in the United Kingdom, bathing with single-use wipes of 2% chlorhexidine gluconate (twice daily), or aqueous 4% chlorhexidine formulation were used on cases. Patients on ventilator support also received mouth washing of 0.2% chlorhexidine or chlorhexidine 1% dental gel, and oral nystatin when oral oropharyngeal colonization was present. Additionally, chlorhexidine impregnated protective disks were used for all central vascular catheter exit sites to reduce line-associated C. auris BSIs. Despite these efforts, C. auris colonization and transmission continued in the facility.

6. Communication

Communication of a person’s C. auris status is key to ensuring that infection control measures are carried out without disruption. When a patient is found to be infected or colonized with C. auris, appropriate communication and education are provided to HCP, so they understand the infection control protocols necessary. HCP should be made aware of the infection control requirements necessary for caring for a patient colonized or infected with C. auris and given sufficient resources to facilitate adherence. Information on C. auris infection or colonization should be communicated whenever patients are transferred to higher or lower levels of care so that the receiving facility is able to continue all infection control measures.

7. Conclusions

C. auris is an emerging multidrug-resistant pathogen that represents a serious threat to healthcare settings globally. This emerging pathogen presents unique issues related to rapid transmission, detection capacity, and specific environmental disinfection needs. However, many of the infection control procedures for C. auris represent standard and fundamental practices, such as hand hygiene or transmission-based precautions. Diligence in detection and infection control can help facilities prevent and control outbreaks of C. auris.