Eye on ID

Watch out for C. auris: It’s not just a problem for infection control

For this Eye on ID, I have turned over the job to Suzanne Bradley to review what is known about a new organism, Candida auris, that has spread over the world in a relatively short time. – Donald Kaye, MD, MACP

Donald Kaye

Candida auris is a new organism that can be resistant to most antifungals. Unlike other Candida species, the primary reservoir of C. auris may be environmental rather than endogenous, with the potential to rapidly spread from patient to patient in health care settings. Therefore, it is important that all clinicians be aware of the existence of C. auris and alert infection control authorities immediately if this organism is suspected.

History of C. auris

Suzanne F. Bradley

C. auris was initially reported in patients diagnosed with chronic otitis media in Korea in 2009. In actuality, the first isolate was found in 1996, but it had been misidentified. Of 15,000 yeasts obtained from 2004 to 2015 by the CDC, only four isolates were confirmed to be C. auris and none occurred before 2013. So, C. auris appears to represent a new species; at least four dominant clades have emerged independently worldwide.

Epidemiology

C. auris has spread across six continents in fewer than 10 years. Multiple cases of infection, with possible transmission, have been reported from health care facilities in Africa (Kenya, South Africa), Australia, East Asia (China, Japan, Singapore, South Korea), South Asia (India, Pakistan), the Middle East (Israel, Kuwait, Oman, Saudi Arabia), North America (Canada, the United States), South and Central America (Columbia, Panama, Venezuela), and Europe (France, Germany, Spain, United Kingdom). Single cases have been identified in Austria, Belgium, Iran, Malaysia, the Netherlands, Norway, Russia, Switzerland and the United Arab Emirates.

As of Feb. 28, 587 confirmed and 30 probable cases of C. auris infection have been reported in the U.S. Most cases have been confined to hospitals and nursing homes in New York (309), New Jersey (104) and Illinois (148). However, sporadic cases have been reported in nine other states including Massachusetts (7), Florida (12), Maryland (3), California (2) and Oklahoma (2), with single cases identified in Connecticut, Indiana, Texas and Virginia. Outbreaks in the New York City area have involved four different clades with transmission of single clones within health care facilities, suggesting that different organisms were introduced into the region by medical travelers, followed by local secondary spread.

Pathogenicity

There are several explanations of why C. auris has emerged and spread so quickly. Lack of effective detection methods with delayed recognition of this yeast has played some role. Unlike other Candida species, an environmental reservoir for C. auris appears to play an important role in its persistence; multiple virulence mechanisms, such as biofilms, may allow it to survive on surfaces and devices. C. auris can remain viable on plastic up to 14 days and on moist surfaces for 7 days. Sources of C. auris environmental contamination found in patient rooms have included a wide variety of surfaces, furniture, catheters, infusion pumps and temperature probes. Therefore, devices should be removed promptly when they are no longer necessary.

Persistent asymptomatic colonization of the host may also help facilitate the spread of this organism in the health care setting. C. auris is not a human commensal. However, once acquired, various body sites may harbor the yeast for up to 3 months or more. Increasing use of antifungal drugs may also have played a role in the selection and emergence of C. auris.

Clinical significance and treatment of C. auris infections

C. auris can cause severe invasive infection in patients with underlying comorbid illnesses, resulting in a high mortality rate of 30% to 60%. Candidemia and sepsis are the most common clinical manifestations reported, but otitis and intra-abdominal and serious wound infections have also occurred. The significance of C. auris isolates from respiratory tract, urine, skin and mucosa is less clear and may reflect asymptomatic colonization. Treatment of asymptomatic colonization or isolates from nonsterile body sites is not recommended.

Invasive infections due to C. auris have been associated with antifungal resistance. It is estimated that 40% of C. auris isolates are resistant to two or more drug classes; 10% are resistant to virtually all antifungal drugs. When choosing a systemic antifungal agent for the treatment of invasive infection, it should be recognized that methods for determining susceptibilities and breakpoints for C. auris are not standardized and are based on expert opinion.

In the U.S., 90% of C. auris isolates appear to be resistant to fluconazole with an MIC90 of at least 64 mg/mL (breakpoint 32 mg/mL). Isolates with an MIC greater than 32 mg/mL are strongly associated with the presence of ERG11, a resistance gene that makes response to fluconazole unlikely. Fluconazole susceptibility patterns may be used as a surrogate to decide if voriconazole and second-generation triazoles may be of benefit or not. The utility of posaconazole and isavuconazole is not known.

Candida auris cultured in a petri dish at the CDC.

Source: Shawn Lockhart/CDC.

Only 5% of U.S. isolates have been found to be resistant to echinocandins, and this drug class is recommended for empiric therapy of invasive infection. The MIC90 for anidulafungin is 0.5 to 1 mg/mL (breakpoint > 4 mg/mL) and micafungin is 0.25 to 2 mg/mL (breakpoint > 4 mg/mL). Resistance to amphotericin B has been seen in 30% of U.S. isolates with an MIC50 of 0.5 to 1 mg/mL and an MIC90 of 2 to 4 mg/mL (breakpoint > 2 mg/mL). If patients fail to respond clinically to treatment with an echinocandin, the addition of empiric amphotericin B therapy can be considered.

Laboratory identification of C. auris

It is important to work closely with local microbiology laboratories when C. auris is suspected to ensure that yeasts from invasive specimens are identified to the species level. Many C. auris isolates are suspected only when species of Candida and other yeasts that are uncommonly seen in most health care settings are reported. The misidentified species that are ultimately proven to be C. auris vary with the yeast identification method used, including: C. haemulonii and C. duobushaemulonii using Vitek 2 YST; Rhodotorula glutinis and C. sake using API 20C; C. haemulonii and C. catenulata using the BD Phoenix yeast identification system; C. famata, C. guilliermondii, C. lusitaniae and C. parapsilosis using Microscan; and C. parapsilosis using RapID Yeast Plus.

Some phenotypic features have helped discriminate C. auris from other yeasts. For example, C. auris does not make germ tubes or form pseudohyphae; the presence of these structures can help differentiate C. auris from C. guilliermondii, C. lusitaniae and C. parapsilosis.C. auris grow better than most yeast when incubated at higher temperatures (40-42°C, or 104-107.6°F); its colonies may appear white, red or purple on CHROMagar.

The most accurate identification of C. auris requires more complex methods that may not be available to many microbiology laboratories. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and other molecular methods, including ribosomal DNA 28S (D1-D2) or internal transcribed spacer region sequencing are currently recommended for the identification of C. auris; PCR-based assays are promising. Suspected isolates should be sent to laboratories that are capable of characterizing C. auris, or to the CDC’s Antibiotic Resistance Laboratory Network. All confirmed C. auris isolates must be reported to CDC (candidaauris@CDC.gov) and state and local health departments.

Preventing spread of C. auris in health care facilities

If Candida species that are unusual for your facility are reported, verify which yeast identification system is being used and if those species might represent misidentified C. auris. If C. auris is suspected, promptly contact infection control to isolate the patient. Isolation should also be done pending results of surveillance cultures, if patients are transferred from facilities known to have C. auris or if patients who had an overnight stay in a country with transmission (or multiple cases) in the past 12 months.

The CDC recommends that patients with possible or confirmed C. auris be placed in a private room in standard and contact precautions with hand hygiene (soap and water or alcohol hand sanitizer), gowns, gloves, and designated equipment. During outbreaks, cohorting of patients and use of designated nursing staff may be considered. Studies of disinfectants active against C. auris are limited; currently, chlorine bleach 1,000 ppm appears to be the most active agent recommended for routine and terminal disinfection of the environment; hydrogen peroxide vapor might also be effective.

A single confirmed case of C. auris should prompt identification of secondary cases and screening of close contacts. Microbiology records should be retrospectively reviewed back to 2015 to detect any cases that might have been missed. All Candida isolates obtained from nonsterile clinical specimens should be identified to the species level for at least 1 month until it is clear that transmission is not occurring in the facility.

Patient screening for C. auris involves obtaining cultures from multiple body sites; highest yields have been noted from the axillae and groin, but cultures of nares, rectum and wounds have been performed. The optimum frequency for screening is not known; during some outbreaks, surveillance cultures for C. auris have been done one to three times weekly. Isolation of C. auris from the skin of normal hosts is very uncommon. The nares and hands of less than 1% of health care workers (HCWs) may become transiently colonized, but persistent colonization with C. auris has not been demonstrated. Screening of HCWs for C. auris is not recommended unless they are linked epidemiologically to a possible transmission event.

Decolonization of patients’ skin and mucosa has been attempted to disrupt C. auris transmission, but the efficacy of this approach has not been established. Chlorhexidine and povidone-iodine appear to be the antiseptics most active against C. auris, but nystatin and terbinafine have also been tried. Whether patients can be taken out of isolation is not known. The CDC has proposed re-screening C. auris-positive patients at 1- to 3-month intervals, but other public health authorities have not made any recommendations about this topic. Two negative cultures for C. auris obtained 1 week apart while off antifungals might be an indication to remove the patient from isolation.

Summary and conclusions

C. auris is a new pathogen that causes severe invasive infections in debilitated patients. Antifungal resistance is common, and patient mortality is high. Transmission from patient to patient is efficient, and disinfection of the environmental reservoir is essential to control this infection. Preventing the spread of C. auris requires awareness on the part of all infectious diseases physicians that this important pathogen could be present in their facility. Clinicians can help facilitate the detection of C. auris by the laboratory and its rapid containment by infection control.

Disclosures: Bradley and Kaye report no relevant financial disclosures.

For this Eye on ID, I have turned over the job to Suzanne Bradley to review what is known about a new organism, Candida auris, that has spread over the world in a relatively short time. – Donald Kaye, MD, MACP

Donald Kaye

Candida auris is a new organism that can be resistant to most antifungals. Unlike other Candida species, the primary reservoir of C. auris may be environmental rather than endogenous, with the potential to rapidly spread from patient to patient in health care settings. Therefore, it is important that all clinicians be aware of the existence of C. auris and alert infection control authorities immediately if this organism is suspected.

History of C. auris

Suzanne F. Bradley

C. auris was initially reported in patients diagnosed with chronic otitis media in Korea in 2009. In actuality, the first isolate was found in 1996, but it had been misidentified. Of 15,000 yeasts obtained from 2004 to 2015 by the CDC, only four isolates were confirmed to be C. auris and none occurred before 2013. So, C. auris appears to represent a new species; at least four dominant clades have emerged independently worldwide.

Epidemiology

C. auris has spread across six continents in fewer than 10 years. Multiple cases of infection, with possible transmission, have been reported from health care facilities in Africa (Kenya, South Africa), Australia, East Asia (China, Japan, Singapore, South Korea), South Asia (India, Pakistan), the Middle East (Israel, Kuwait, Oman, Saudi Arabia), North America (Canada, the United States), South and Central America (Columbia, Panama, Venezuela), and Europe (France, Germany, Spain, United Kingdom). Single cases have been identified in Austria, Belgium, Iran, Malaysia, the Netherlands, Norway, Russia, Switzerland and the United Arab Emirates.

As of Feb. 28, 587 confirmed and 30 probable cases of C. auris infection have been reported in the U.S. Most cases have been confined to hospitals and nursing homes in New York (309), New Jersey (104) and Illinois (148). However, sporadic cases have been reported in nine other states including Massachusetts (7), Florida (12), Maryland (3), California (2) and Oklahoma (2), with single cases identified in Connecticut, Indiana, Texas and Virginia. Outbreaks in the New York City area have involved four different clades with transmission of single clones within health care facilities, suggesting that different organisms were introduced into the region by medical travelers, followed by local secondary spread.

Pathogenicity

There are several explanations of why C. auris has emerged and spread so quickly. Lack of effective detection methods with delayed recognition of this yeast has played some role. Unlike other Candida species, an environmental reservoir for C. auris appears to play an important role in its persistence; multiple virulence mechanisms, such as biofilms, may allow it to survive on surfaces and devices. C. auris can remain viable on plastic up to 14 days and on moist surfaces for 7 days. Sources of C. auris environmental contamination found in patient rooms have included a wide variety of surfaces, furniture, catheters, infusion pumps and temperature probes. Therefore, devices should be removed promptly when they are no longer necessary.

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Persistent asymptomatic colonization of the host may also help facilitate the spread of this organism in the health care setting. C. auris is not a human commensal. However, once acquired, various body sites may harbor the yeast for up to 3 months or more. Increasing use of antifungal drugs may also have played a role in the selection and emergence of C. auris.

Clinical significance and treatment of C. auris infections

C. auris can cause severe invasive infection in patients with underlying comorbid illnesses, resulting in a high mortality rate of 30% to 60%. Candidemia and sepsis are the most common clinical manifestations reported, but otitis and intra-abdominal and serious wound infections have also occurred. The significance of C. auris isolates from respiratory tract, urine, skin and mucosa is less clear and may reflect asymptomatic colonization. Treatment of asymptomatic colonization or isolates from nonsterile body sites is not recommended.

Invasive infections due to C. auris have been associated with antifungal resistance. It is estimated that 40% of C. auris isolates are resistant to two or more drug classes; 10% are resistant to virtually all antifungal drugs. When choosing a systemic antifungal agent for the treatment of invasive infection, it should be recognized that methods for determining susceptibilities and breakpoints for C. auris are not standardized and are based on expert opinion.

In the U.S., 90% of C. auris isolates appear to be resistant to fluconazole with an MIC90 of at least 64 mg/mL (breakpoint 32 mg/mL). Isolates with an MIC greater than 32 mg/mL are strongly associated with the presence of ERG11, a resistance gene that makes response to fluconazole unlikely. Fluconazole susceptibility patterns may be used as a surrogate to decide if voriconazole and second-generation triazoles may be of benefit or not. The utility of posaconazole and isavuconazole is not known.

Candida auris cultured in a petri dish at the CDC.

Source: Shawn Lockhart/CDC.

Only 5% of U.S. isolates have been found to be resistant to echinocandins, and this drug class is recommended for empiric therapy of invasive infection. The MIC90 for anidulafungin is 0.5 to 1 mg/mL (breakpoint > 4 mg/mL) and micafungin is 0.25 to 2 mg/mL (breakpoint > 4 mg/mL). Resistance to amphotericin B has been seen in 30% of U.S. isolates with an MIC50 of 0.5 to 1 mg/mL and an MIC90 of 2 to 4 mg/mL (breakpoint > 2 mg/mL). If patients fail to respond clinically to treatment with an echinocandin, the addition of empiric amphotericin B therapy can be considered.

PAGE BREAK

Laboratory identification of C. auris

It is important to work closely with local microbiology laboratories when C. auris is suspected to ensure that yeasts from invasive specimens are identified to the species level. Many C. auris isolates are suspected only when species of Candida and other yeasts that are uncommonly seen in most health care settings are reported. The misidentified species that are ultimately proven to be C. auris vary with the yeast identification method used, including: C. haemulonii and C. duobushaemulonii using Vitek 2 YST; Rhodotorula glutinis and C. sake using API 20C; C. haemulonii and C. catenulata using the BD Phoenix yeast identification system; C. famata, C. guilliermondii, C. lusitaniae and C. parapsilosis using Microscan; and C. parapsilosis using RapID Yeast Plus.

Some phenotypic features have helped discriminate C. auris from other yeasts. For example, C. auris does not make germ tubes or form pseudohyphae; the presence of these structures can help differentiate C. auris from C. guilliermondii, C. lusitaniae and C. parapsilosis.C. auris grow better than most yeast when incubated at higher temperatures (40-42°C, or 104-107.6°F); its colonies may appear white, red or purple on CHROMagar.

The most accurate identification of C. auris requires more complex methods that may not be available to many microbiology laboratories. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and other molecular methods, including ribosomal DNA 28S (D1-D2) or internal transcribed spacer region sequencing are currently recommended for the identification of C. auris; PCR-based assays are promising. Suspected isolates should be sent to laboratories that are capable of characterizing C. auris, or to the CDC’s Antibiotic Resistance Laboratory Network. All confirmed C. auris isolates must be reported to CDC (candidaauris@CDC.gov) and state and local health departments.

Preventing spread of C. auris in health care facilities

If Candida species that are unusual for your facility are reported, verify which yeast identification system is being used and if those species might represent misidentified C. auris. If C. auris is suspected, promptly contact infection control to isolate the patient. Isolation should also be done pending results of surveillance cultures, if patients are transferred from facilities known to have C. auris or if patients who had an overnight stay in a country with transmission (or multiple cases) in the past 12 months.

The CDC recommends that patients with possible or confirmed C. auris be placed in a private room in standard and contact precautions with hand hygiene (soap and water or alcohol hand sanitizer), gowns, gloves, and designated equipment. During outbreaks, cohorting of patients and use of designated nursing staff may be considered. Studies of disinfectants active against C. auris are limited; currently, chlorine bleach 1,000 ppm appears to be the most active agent recommended for routine and terminal disinfection of the environment; hydrogen peroxide vapor might also be effective.

PAGE BREAK

A single confirmed case of C. auris should prompt identification of secondary cases and screening of close contacts. Microbiology records should be retrospectively reviewed back to 2015 to detect any cases that might have been missed. All Candida isolates obtained from nonsterile clinical specimens should be identified to the species level for at least 1 month until it is clear that transmission is not occurring in the facility.

Patient screening for C. auris involves obtaining cultures from multiple body sites; highest yields have been noted from the axillae and groin, but cultures of nares, rectum and wounds have been performed. The optimum frequency for screening is not known; during some outbreaks, surveillance cultures for C. auris have been done one to three times weekly. Isolation of C. auris from the skin of normal hosts is very uncommon. The nares and hands of less than 1% of health care workers (HCWs) may become transiently colonized, but persistent colonization with C. auris has not been demonstrated. Screening of HCWs for C. auris is not recommended unless they are linked epidemiologically to a possible transmission event.

Decolonization of patients’ skin and mucosa has been attempted to disrupt C. auris transmission, but the efficacy of this approach has not been established. Chlorhexidine and povidone-iodine appear to be the antiseptics most active against C. auris, but nystatin and terbinafine have also been tried. Whether patients can be taken out of isolation is not known. The CDC has proposed re-screening C. auris-positive patients at 1- to 3-month intervals, but other public health authorities have not made any recommendations about this topic. Two negative cultures for C. auris obtained 1 week apart while off antifungals might be an indication to remove the patient from isolation.

Summary and conclusions

C. auris is a new pathogen that causes severe invasive infections in debilitated patients. Antifungal resistance is common, and patient mortality is high. Transmission from patient to patient is efficient, and disinfection of the environmental reservoir is essential to control this infection. Preventing the spread of C. auris requires awareness on the part of all infectious diseases physicians that this important pathogen could be present in their facility. Clinicians can help facilitate the detection of C. auris by the laboratory and its rapid containment by infection control.

PAGE BREAK

Disclosures: Bradley and Kaye report no relevant financial disclosures.