Candida auris: Infectious substances pathogen safety data sheet

For more information on Candida auris, see the following:

• Interim recommendations for infection prevention and control

Section I – Infectious agent

Name

Candida auris

Agent type

Fungus

Taxonomy

Family

Metschnikowiaceae^{Footnote 1Footnote 2Footnote 3}

Genus

Candida

Species

auris

Synonym or cross-reference

Candidemia, candidiasis.

Characteristics

Brief description

Candida auris is an ascomycete yeast species first described in Japan in 2009^{Footnote 4Footnote 5}. Cells are approximately 2.0-3.0 x 2.5-5.0 µm in size and exhibit morphological plasticity under different culture conditions, including round-to-ovoid, elongated, and filamentous (hyphal or pseudohyphal-like) forms^{Footnote 4Footnote 6Footnote 7}. The haploid genome is approximately 12.5 Mb, with a G+C content of nearly 45% and an estimated 6,500-8,500 protein-coding sequences^{Footnote 5}. Since 2009, 5 genetically diverse clades of C. auris have been identified based on genetic and genomic information and locations of first isolates: the South Asia Clade (I), the East Asia Clade (II), the South Africa Clade (III), the South America Clade (IV), and most recently in 2019, the Iran Clade (V)^{Footnote 4Footnote 8}.

Properties

C. auris usually grows between 30-42°C (optimum 37-40°C), although certain isolates may grow at 47°C^{Footnote 6Footnote 9}. Notable virulence factors include hyphae formation, production of phospholipases and proteinases, adherence, biofilm formation, cellular morphology (aggregating and non-aggregating forms), thermotolerance and osmotolerance^{Footnote 7Footnote 10}. C. auris is a budding yeast; however, some strains may not release daughter cells after budding, resulting in aggregates of pseudohyphal-like cells with high physical resistance, which may facilitate persistence in tissues and on surfaces^{Footnote 6Footnote 7Footnote 11}. Although both cell types can form biofilms, non-aggregating isolates develop stronger biofilms and are therefore associated with increased virulence and pathogenicity relative to aggregating cells^{Footnote 4Footnote 11}. The genome also encodes several genes that may confer resistance if mutated or overexpressed, such as ATP-binding cassette transporters and major facilitator superfamily members, suggesting a potential efflux-mediated resistance mechanism to several antifungal agents^{Footnote 5Footnote 6Footnote 11}.

Section II – Hazard identification

Pathogenicity and toxicity

C. auris infection is associated with a wide range of clinical presentations. It is commonly involved in hospital-acquired candidemia (i.e., blood infection), characterized by fever, general weakness, malaise, hypotension, elevated acute phase reactants, and leukocytosis, which may progress to cardiogenic and septic shock, seizures, brain ring-enhancing lesions, multi-organ failure, and death^{Footnote 12Footnote 13Footnote 14Footnote 15}. Complications following dissemination (i.e., invasive infection) include ventriculitis and meningitis, with symptoms including vomiting, loss of consciousness, recurring episodes of fever and seizures, spastic posture, increased muscle tone, dilated pupils, and tachycardia, as well as spondylodiscitis^{Footnote 16Footnote 17Footnote 18}. A case of recalcitrant cerebrospinal fluid shunt infection due to C. auris was reported, in which the patient presented with sudden onset of altered sensorium followed by high fever, enlarged ventricular lining, leukocytosis, and increased C-reactive protein count^{Footnote 19}. C. auris otomycosis has been reported, with cases of malignant otitis characterized by chronic and persistent otalgia, pruritus, otorrhea, inflammation, redness, tinnitus, hearing loss, and tympanic membrane perforation^{Footnote 20Footnote 21Footnote 22}. Otomastoiditis associated with C. auris infection may present as chronic pontine haemorrhage, fever, stupor, and bloody ear discharge^{Footnote 23}. Musculoskeletal manifestations include intra-articular infection and osteomyelitis^{Footnote 24Footnote 25Footnote 26}. Clinical manifestations of osteomyelitis associated with C. auris infection may include chronic discharging bony sinus, adjacent abscesses^{Footnote 24}, bony erosion and fragmentation associated with alterations in bone density, and severe myositis^{Footnote 25}. Pericarditis associated with C. auris is characterized by shortness of breath, cough, expectoration, interstitial edema, cardiomegaly, tachycardia, and leukocytosis, which may lead to septic shock and death^{Footnote 27}. C. auris has also been implicated in complicated pleural effusions and intra-abdominal infections, urinary tract infections, vulvovaginitis, skin abscesses, and wound infections; however, isolation of C. auris from non-sterile body sites such as the lungs, the genitourinary tract, the skin, and soft tissue may represent colonization rather than true infection^{Footnote 7Footnote 10}.

Mortality rates vary widely according to geographical region and clade^{Footnote 5}. Cases from Asia and the United States have reported mortality rates over 50% for invasive infections, whereas in Colombia, 30-day mortality rate was 35%^{Footnote 5}. Crude in-hospital mortality rates for C. auris candidemia are estimated to range from 30-72%^{Footnote 7}. Overall attributable mortality rate of C. auris is unclear due to concurrent comorbidities; limited estimates range between 22-67%^{Footnote 28}. C. auris candidemia may occur in up to 25% of colonized critically ill patients^{Footnote 29}.

Epidemiology

C. auris was first described as a novel Candida species in 2009 after it was isolated from the external ear canal discharge of a 70-year-old Japanese woman^{Footnote 4Footnote 5Footnote 7}. The first 3 cases of candidemia associated with C. auris were reported from South Korea in 2011 but were initially misidentified; 1 case occurred in 1996 and 2 cases occurred in 2009^{Footnote 34}. As of February 15, 2021, over 5,000 cases of infection were reported in 47 countries from 6 continents, with large numbers of cases in South Africa, the United States, India, Spain, the United Kingdom, South Korea, Colombia, and Pakistan^{Footnote 4Footnote 5Footnote 30}. C. auris is now considered endemic in some parts of the United States^{Footnote 31}, Spain^{Footnote 32}, India^{Footnote 33}, and South Africa^{Footnote 12}.

Since 2012, over 30 cases of C. auris infection or colonization have been reported in hospitalized patients in 6 Canadian provinces^{Footnote 34}. The first case of multidrug-resistant C. auris in Canada was reported in May 2017 in a patient with recent hospitalization in India^{Footnote 35}. In August 2017, C. auris was isolated in British Columbia in a returning Canadian traveler with a history of hospitalization in India^{Footnote 36}. Early in 2018, 2 further colonization cases were reported from the same hospital as the first case in British Columbia^{Footnote 41}. The first reported hospital outbreak in Canada occurred in 2018, in which 4 cases were identified in the ICU of a community healthcare facility in the Greater Vancouver area over a 2-month period^{Footnote 41}.

The first reported cases of C. auris infection in the United States occurred between May 2013 and August 2016 and were reported from the states of Illinois (n = 2), Maryland (n = 1), New Jersey (n = 1), and New York (n = 3)^{Footnote 37}. Clinical cases increased by 58% from 2019 (478 cases) to 2020 (757 cases) and by an additional 95% in 2021 (1,474 cases)^{Footnote 38}. In 2022, 2,377 clinical cases were reported across 29 states, a 497% increase from 2019^{Footnote 43}. As of December 31, 2022, a total of 5,654 clinical cases and 13,163 screening cases have been recorded in the United States^{Footnote 43}.

The first large-scale C. auris outbreak in Europe occurred in a cardio-thoracic hospital in London between April 2015 and November 2016, involving 72 patients^{Footnote 39}. Several outbreaks were reported in Austria, Belgium, France, Germany, Greece, Italy, Norway, Russia, Spain, Switzerland, the Netherlands, and the United Kingdom between 2013 and 2019, comprising more than 600 cases of infection or colonization^{Footnote 8Footnote 37}.

In South Africa, C. auris is the causative agent in 10% of candidemia cases^{Footnote 12}. Large outbreaks were reported in over 94 hospitals between 2012-2016 for a total of 1,692 confirmed or probable cases of C. auris infection^{Footnote 40}. From September 2010 through December 2016, 77 cases of C. auris candidemia were reported at a referral hospital in Kenya, accounting for 38% of candidemia cases^{Footnote 41}.

In India, a total of 62 cases were reported across several healthcare facilities during 2009-2017^{Footnote 38Footnote 42Footnote 43Footnote 44}. C. auris was implicated in 5% of candidemia cases in 27 intensive care units (ICUs), although other Indian healthcare facilities reported incidences of 17.5-30% between 2011 and 2017^{Footnote 12Footnote 47Footnote 48}. In Pakistan, a total of 124 cases were reported in at least 3 tertiary care hospitals between January 2012 and October 2018^{Footnote 45Footnote 46Footnote 49}. Between 1996 and 2018, several cases were reported in China (n = 15), Japan (n = 1), Malaysia (n = 1), Singapore (n = 3), and South Korea (n = 61) following nosocomial outbreaks^{Footnote 8}.

Cases of C. auris have been reported in COVID-19 patients in Brazil, Colombia, Guatemala, Lebanon, Mexico, Peru, Panama, and the United States^{Footnote 47Footnote 48}. Outbreaks have also been reported in Australia, Iran, Israel, Kuwait, Oman, Saudi Arabia, the United Arab Emirates, and Venezuela^{Footnote 8}.

As with other Candida species, predisposing factors for C. auris infection include extremes of age, hospitalization, particularly an ICU stay, presence of indwelling medical devices (e.g., central venous catheter), mechanical ventilation, parenteral nutrition, immunosuppression, medical comorbidities (e.g., diabetes, hypertension, chronic lung or kidney disease), hemodialysis, neutropenia, concomitant bacteremia, recent surgery, and exposure to broad-spectrum antibiotics or antifungals, admission in healthcare facilities in regions of C. auris endemicity, and co-colonization with a carbapenemase-producing organism^{Footnote 4Footnote 10Footnote 11Footnote 12Footnote 49}.

Host range

Natural host(s)

Humans^{Footnote 1}.

Other host(s)

Experimentally infected hosts include mice, greater wax moths (Galleria mellonella), common fruit flies (Drosophila melanogaster), and roundworms (Caenorhabditis elegans)^{Footnote 1}.

Infectious dose

Unknown in humans. An infectious dose of 10⁷ colony-forming units (CFU) administered intravenously through the lateral tail vein resulted in 21-day mortality rates of 96% for the South American clade, 80% for the South Asian clade, 45% for the South African clade, and 44% for the East Asian clade in neutropenic murine bloodstream infection models^{Footnote 28}.

Incubation period

Up to 41-61 days^{Footnote 50}. Shedding from the skin occurs at a rate of approximately 10⁶ cells/hour for unknown duration^{Footnote 6}.

Communicability

C. auris has a propensity to colonize skin surfaces and can be shed in healthcare settings where it survives for prolonged periods^{Footnote 6Footnote 11}. Although the mode of transmission can vary, early evidence suggests that C. auris is mainly transmitted by direct contact with mucous membranes or damaged skin, as most reports of C. auris infection or colonization are associated with use of central venous or urinary catheters, recent surgery, and parenteral nutrition^{Footnote 51Footnote 52}. Transmission by direct (i.e., intimate) and indirect (i.e., fomites) contact has frequently been reported in outbreak settings, including transmission through shared medical equipment and a possible case of vertical transmission from mother to newborn^{Footnote 6Footnote 53}. Injection is also a possible mode of transmission, as C. auris has caused candidemia concurrent with catheter use^{Footnote 54}.

Section III – Dissemination

Reservoir

Unknown.

Zoonosis

Unknown.

Vectors

Unknown.

Section IV – Stability and viability

Drug susceptibility/resistance

Variable susceptibility to voriconazole and other second-generation azoles, amphotericin B, and echinocandins (e.g., anidulafungin, caspofungin, micafungin)^{Footnote 55}.

Rates of drug resistance vary widely by geographic region^{Footnote 4Footnote 10Footnote 12}. Globally, over 90% of C. auris strains are resistant to fluconazole, with clade-specific rates of resistance ranging from 14% among isolates in Colombia to over 90% in South Asian clade isolates^{Footnote 10Footnote 12}. A range of 3-73% of global isolates are resistant to voriconazole^{Footnote 10Footnote 47Footnote 56}. Amphotericin B resistance rates vary from 8-37%, whereas echinocandin resistance occurs in approximately 2-7% of isolates^{Footnote 10Footnote 12Footnote 55Footnote 57}. Forty-seven percent of C. auris isolates identified from a tertiary care hospital in South India were resistant to flucytosine^{Footnote 47}.

Multidrug resistance to 2 antifungal classes has been reported in 41% of global isolates^{Footnote 12Footnote 55}. Approximately 4% of strains are resistant to all 3 classes of antifungal agents (azoles, polyenes, and echinocandins)^{Footnote 55Footnote 57}.

Susceptibility to disinfectants

C. auris is susceptible to sodium hypochlorite at various concentrations (0.39-10% or 1,000-10,000 ppm chlorine), 0.125-1.5% chlorhexidine gluconate, 2% chlorhexidine gluconate in 70% isopropyl alcohol, 0.07-10% povidone-iodine, 1.4% hydrogen peroxide, activated hydrogen peroxide (AHP), 11% hydrogen peroxide in silver nitrate, 5% phenol, 2% glutaraldehyde, 29.4% ethyl alcohol, and 2000 ppm peracetic acid^{Footnote 5Footnote 58Footnote 59Footnote 60}. It is considered resistant to disinfection with quaternary ammonium compounds and alcohols^{Footnote 39Footnote 59}. Products intended to disinfect high-contact environmental surfaces should be effective within 5 minutes^{Footnote 58}.

Physical inactivation

C. auris can be inactivated by heat treatment at 56°C for 1 hour^{Footnote 61}. C. auris is susceptible to low pH (pH 2) and stress combinations imposed by hospital laundering protocol (pH > 12 plus heat shock at 60°C or above for 5 minutes)^{Footnote 9}. C. auris may be inactivated by ultraviolet germicidal irradiation (UVGI), with 99.999% inactivation noted in suspensions of 10⁶ cells/mL exposed to 11 UV doses between 103-192 mJ/cm² at 254 nms^{Footnote 62}. However, data on susceptibility of C. auris to ultraviolet light are limited and parameters required for effective inactivation are not well understood^{Footnote 63}.

Survival outside host

C. auris is known to survive on human and environmental surfaces for several weeks^{Footnote 1}. C. auris may colonize and persist on plastic surfaces for more than 28 days^{Footnote 64}. C. auris can also survive on cotton textile, polystyrene, paper, aluminum, glass, and latex surfaces for at least 1 week at room temperatures^{Footnote 65}.

Section V – First aid/medical

Surveillance

C. auris can be misidentified as several different organisms by routine laboratory biochemical testing methods^{Footnote 12}. It can be accurately identified using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry instruments with databases that include C. auris, or by molecular-based sequencing methods^{Footnote 12}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Antifungal susceptibility testing should be performed on C. auris isolates as levels of antifungal resistance may vary widely across isolates^{Footnote 66}. Tentative susceptibility breakpoints for C. auris have been published by the Centers for Disease Control and Prevention^{Footnote 66}. In adults, anidulafungin, caspofungin, and micafungin are considered first-line treatment options, while liposomal amphotericin B is an alternative treatment regimen^{Footnote 55}. In children ≥ 2 months of age recommended first-line agents are caspofungin and micafungin, and liposomal amphotericin B is an alternative option^{Footnote 55}. Amphotericin B deoxycholate is recommended for first-line treatment in children less than 2 months of age, whereas liposomal amphotericin B, caspofungin, and micafungin may be used as alternatives^{Footnote 55}. Alternative therapy may be considered in cases of treatment failure with first-line agents or in patients with persistent candidemia (greater than 5 days)^{Footnote 55}. If possible, removal of central catheters or other invasive devices may resolve persistent candidemia and improve clinical outcomes^{Footnote 7}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine currently available. However, the C. albicans vaccine NDV-3A has successfully immunized mice and exhibited an additive protective effect when combined with micafungin^{Footnote 67}.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Post-exposure prophylaxis with micafungin may be considered in low-birthweight, preterm neonates in nosocomial settings with high prevalence of C. auris^{Footnote 33}. However, prophylactic antifungal therapy should be avoided or administered with caution as over-use may select for multidrug-resistant C. auris^{Footnote 6}. Colonization may last months or persist indefinitely^{Footnote 59}. There is currently no established protocol for decolonization of patients with C. auris^{Footnote 55}, although chlorohexidine washes may be used for topical decolonization^{Footnote 58}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

None reported.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, cerebrospinal fluid, bone, ear discharge, pancreatic fluid, pericardial fluid, peritoneal fluid, pleural fluid, respiratory secretions (including sputum and bronchoalveolar lavage), skin and soft tissue samples (both tissue and swab cultures), bile, urine, and vaginal secretions^{Footnote 4Footnote 32}.

Primary hazards

Exposure of mucous membranes/skin to infectious material and exposure to infectious material on fomites are the primary hazards associated with exposure to C. auris^{Footnote 6Footnote 31Footnote 32}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

Candida auris is a Risk Group 2 (RG2) Human Pathogen and RG1 Animal Pathogen^{Footnote 68}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS is to be followed. The personal protective equipment could include the use of a lab coat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, PM rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

The use of needles and syringes is to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes is to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain Candida auris, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area/third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

Containment Level 2: The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Candida auris require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act, and
• Human Pathogens and Toxins Regulations

Last file update

April 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2023, Canada