Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

On the emergence, spread and resistance of Candida auris: host, pathogen and environmental tipping points.

Over a decade ago, a multidrug-resistant nosocomial fungus Candida auris emerged worldwide and has since become a significant challenge for clinicians and microbiologists across the globe. A resilient pathogen, C. auris survives harsh disinfectants, desiccation and high-saline environments. It readily colonizes the inanimate environment, susceptible patients and causes invasive infections that exact a high toll. Prone to misidentification by conventional microbiology techniques, C. auris rapidly acquires multiple genetic determinants that confer multidrug resistance. Whole-genome sequencing has identified four distinct clades of C. auris, and possibly a fifth one, in circulation. Even as our understanding of this formidable pathogen grows, the nearly simultaneous emergence of its distinct clades in different parts of the world, followed by their rapid global spread, remains largely unexplained. We contend that certain host-pathogen-environmental factors have been evolving along adverse trajectories for the last few decades, especially in regions where C. auris originally appeared, until these factors possibly reached a tipping point to compel the evolution, emergence and spread of C. auris. Comparative genomics has helped identify several resistance mechanisms in C. auris that are analogous to those seen in other Candida species, but they fail to fully explain how high-level resistance rapidly develops in this yeast. A better understanding of these unresolved aspects is essential not only for the effective management of C. auris patients, hospital outbreaks and its global spread but also for forecasting and tackling novel resistant pathogens that might emerge in the future. In this review, we discuss the emergence, spread and resistance of C. auris, and propose future investigations to tackle this resilient pathogen.

Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies.

Candida auris is an emerging multi-drug-resistant human fungal pathogen. C. auris skin colonization results in environmental shedding, which underlies hospital transmissions, and predisposes patients to subsequent infections. We developed a murine skin topical exposure model for C. auris to dissect risk factors for colonization and to test interventions that might protect patients. We demonstrate that C. auris establishes long-term residence within the skin tissue compartment, which would elude clinical surveillance. The four clades of C. auris, with geographically distinct origins, differ in their abilities to colonize murine skin, mirroring epidemiologic findings. The IL-17 receptor signaling and specific arms of immunity protect mice from long-term C. auris skin colonization. We further determine that commonly used chlorhexidine antiseptic serves as a protective and decolonizing agent against C. auris. This translational model facilitates an integrated approach to develop strategies to combat the unfolding global outbreaks of C. auris and other skin-associated microbial pathogens.

Molecular characterisation and clinical outcomes of Candida auris infection: Single-centre experience in Saudi Arabia.

BACKGROUND: Candida auris is a difficult-to-diagnose multidrug-resistant yeast that can cause invasive infections with high mortality. Since emerging in 2009, this pathogen has been associated with numerous outbreaks around the world. Whole genome sequencing (WGS) is instrumental for understanding the emergence and local transmission of this pathogen. OBJECTIVES: To describe the clinical, molecular characteristics of Candida auris infection and clinical outcome in our centre. PATIENTS AND METHODS: Patients with positive cultures for Candida auris were identified in a microbiology database. Clinical characteristics and antifungal susceptibility were obtained. Isolates were sent to the US CDC for whole genome sequencing. RESULTS: Seven unique patients with eight different isolates were identified. Seven isolates were sent to the US CDC for whole genome sequencing. None of the patients had bloodstream infection. Thirty-day mortality was higher in infected patients compared with those who were colonised. Seven of the eight isolates were resistant to both fluconazole, and five were resistant to amphotericin B. WGS analysis demonstrated that the seven isolates belonged to the South Asian clade but formed two distinct subclades suggesting two independent introductions and ongoing transmission within the facility. CONCLUSIONS: Candida auris is associated with a high mortality rate in infected patients. Strict infection control measures and surveillance for asymptomatic cases are warranted to halt ongoing transmission.

The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting.

Candida auris is an emerging pathogenic yeast of significant clinical concern because of its frequent intrinsic resistance to fluconazole and often other antifungal drugs and the high mortality rates associated with systemic infections. Furthermore, C. auris has a propensity for persistence and transmission in health care environments. The reasons for this efficient transmission are not well understood, and therefore we tested whether enhanced resistance to environmental stresses might contribute to the ability of C. auris to spread in health care environments. We compared C. auris to other pathogenic Candida species with respect to their resistance to individual stresses and combinations of stresses. Stress resistance was examined using in vitro assays on laboratory media and also on hospital linen. In general, the 17 C. auris isolates examined displayed similar degrees of resistance to oxidative, nitrosative, cationic and cell wall stresses as clinical isolates of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae and C. kefyr. All of the C. auris isolates examined were more sensitive to low pH (pH 2, but not pH 4) compared to C. albicans, but were more resistant to high pH (pH 13). C. auris was also sensitive to low pH, when tested on contaminated hospital linen. Most C. auris isolates were relatively thermotolerant, displaying significant growth at 47°C. Furthermore, C. auris was relatively resistant to certain combinations of combinatorial stress (e.g., pH 13 plus 47°C). Significantly, C. auris was sensitive to the stress combinations imposed by hospital laundering protocol (pH > 12 plus heat shock at >80°C), suggesting that current laundering procedures are sufficient to limit the transmission of this fungal pathogen via hospital linen.

Persistence of Candida auris on latex and nitrile gloves with transmission to sterile urinary catheters‡.

Candida auris' ability to persist on contaminated gloves and transmit to urinary catheters was evaluated. 105 and 103 cfu/ml suspensions of eight Candida species including C. auris were inoculated on latex and nitrile gloves fingertips and touched on agar surface at different time intervals. Urinary catheter piece, touched by latex glove carrying Candida spp. suspensions at various time intervals, was cultured by roll-plate method. C.auris persisted on latex gloves at both 105 and 103 cfu/ml up to 3 minutes and could be transmitted from both wet and dry contaminated gloves to catheters. Proper glove use with strict hand hygiene should be advocated in settings with ongoing C.auris transmission.

Candida auris outbreak: Mortality, interventions and cost of sustaining control.

OBJECTIVE: Candida auris has recently emerged as a global cause of multidrug resistant fungal outbreaks. An outbreak occurred at a tertiary care center in London in 2016. Transmission characteristics, interventions, patient outcomes and cost of resources are described. METHODS: Outbreak interventions included patient isolation, contact screening, single-use equipment, environmental screening and decontamination, staff education, and enhanced surveillance. Risk factors for infection were recorded. Survival probabilities of patients with C. auris and other Candida bloodstream infections (BSI) were calculated. Antifungal susceptibility and epidemiological typing were performed. Actual and opportunity costs of interventions were determined. RESULTS: 34 patients acquired the organism including 8 with BSI. Clinical infection was significantly associated with prolonged hospital stay, haemodialysis and antifungal therapy. Variable susceptibility to amphotericin and the triazoles was seen and isolates clustered with the South Asian strains. No significant difference was detected in the survival probabilities of C. auris BSI compared to other candidemias. Outbreak control cost in excess of £1 million and £58,000/month during the subsequent year. CONCLUSION: C. auris outbreaks can be controlled by a concerted infection control strategy but can be expensive. Transmission maybe prolonged due to patient movements and unidentified transmission mechanisms.

Is Candida auris here to stay? An interview with Dimitrios Kontoyiannis.

In this exclusive interview, Dimitrios P Kontoyiannis discusses current mycology hot topic, Candida auris. With a focus on the current knowns and unknowns for the pathogenesis, resistance and transmission of this emerging fungal pathogen, in addition to a look at therapeutics and future perspectives. This interview was conducted by Ellen Colvin, Commissioning Editor of Future Microbiology. Dimitrios P Kontoyiannis is the Texas 4000 distinguished endowed professor and deputy head in the Division of Internal Medicine at MD Anderson Cancer Center in Houston (TX, USA). Dr Kontoyiannis has authored over 550 peer-reviewed manuscripts and has given over 330 lectures in national and international conferences and academic institutions in the USA and abroad. He is considered a leading mycology expert world-wide with an H index of 101 and over 43,000 citations. His research group is credited for many and sustained contributions to clinical, translational and experimental mycology. He is the recipient of many national and international awards and is the past president elect of Immunocompromised Host Society (2016-2018).

High-resolution fingerprinting of Candida parapsilosis isolates suggests persistence and transmission of infections among neonatal intensive care unit patients in Kuwait.

Candida parapsilosis causes ~35% of all candidemia cases in neonates. High-resolution fingerprinting of C. parapsilosis isolates from neonatal intensive care unit (NICU) patients in Maternity Hospital (MH) was performed to identify epidemiologically related strains. Sixty-eight bloodstream/colonizing strains isolated from 59 NICU patients, two isolates from health care workers (HCWs) from MH and 18 bloodstream isolates from two other hospitals were used. Six microsatellite markers were employed, isolates were assigned a numerical microsatellite genotype (MSG), dendrogram was constructed and similarities between genotypes were visualized by minimum spanning tree. Fifty bloodstream isolates from MH yielded 37 MSGs with 20 isolates clustering in 7 MSGs. Duplicate isolates and colonizing strains yielded same/highly similar MSG as bloodstream isolates. Colonizing strains from two non-candidemia patients yielded unique MSGs while others belonged to a cluster. All isolates from HCWs and from two other hospitals belonged to unique MSGs. Cluster isolates came from patients in NICU-1 or from neonates in NICU-1 and other NICUs. Clonal complexes comprising closely related genotypes indicative of microevolution were also detected. Our data show that some C. parapsilosis strains have persisted in MH environment over several years and these endemic genotypes were transmitted to other patients in NICU-1 and/or other nearby NICUs.

Susceptibility of Candida auris and Candida albicans to 21 germicides used in healthcare facilities.

Candida auris is an emerging fungal pathogen that is often resistant to major classes of antifungal drugs. It is considered a serious global health threat because it can cause severe infections with frequent mortality in more than a dozen countries. It can survive on healthcare environmental surfaces for at least 7 days and can cause outbreaks in healthcare facilities. Clearly, infection prevention strategies, such as surface disinfection, will be essential to controlling Candida transmission. Unfortunately, data on the activity of antiseptics and disinfectants used in healthcare to inactivate this pathogen are limited.1-5 In this study, we investigated 12 different disinfectants (ie, 8 low- and intermediate-level disinfectants in 2 dilutions of sodium hypochlorite and 5 high-level disinfectants/chemical sterilants) and 9 antiseptics commonly used in healthcare facilities for their antimicrobial activity against C. auris and C. albicans.

Candida auris: The recent emergence of a multidrug-resistant fungal pathogen.

Candida auris is an emerging multidrug-resistant yeast that causes serious invasive infections with high mortality. It was first discovered in 2009, and since then, individual cases or outbreaks have been reported from over 20 countries on five continents. Controlling C. auris is challenging for several reasons: (1) it is resistant to multiple classes of antifungals, (2) it can be misidentified as other yeasts by commonly available identification methods, and (3) because of its ability to colonize patients perhaps indefinitely and persist in the healthcare environment, it can spread between patients in healthcare settings. The transmissibility and high levels of antifungal resistance that are characteristic of C. auris set it apart from most other Candida species. A robust response that involves the laboratory, clinicians, and public health agencies is needed to identify and treat infections and prevent transmission. We review the global emergence, biology, challenges with laboratory identification, drug resistance, clinical manifestations, treatment, risk factors for infection, transmission, and control of C. auris.

A Candida auris Outbreak and Its Control in an Intensive Care Setting.

BACKGROUND: Candida auris is an emerging and multidrug-resistant pathogen. Here we report the epidemiology of a hospital outbreak of C. auris colonization and infection. METHODS: After identification of a cluster of C. auris infections in the neurosciences intensive care unit (ICU) of the Oxford University Hospitals, United Kingdom, we instituted an intensive patient and environmental screening program and package of interventions. Multivariable logistic regression was used to identify predictors of C. auris colonization and infection. Isolates from patients and from the environment were analyzed by whole-genome sequencing. RESULTS: A total of 70 patients were identified as being colonized or infected with C. auris between February 2, 2015, and August 31, 2017; of these patients, 66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C. auris infections developed in 7 patients. When length of stay in the neurosciences ICU and patient vital signs and laboratory results were controlled for, the predictors of C. auris colonization or infection included the use of reusable skin-surface axillary temperature probes (multivariable odds ratio, 6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18; P=0.01). C. auris was rarely detected in the general environment. However, it was detected in isolates from reusable equipment, including multiple axillary skin-surface temperature probes. Despite a bundle of infection-control interventions, the incidence of new cases was reduced only after removal of the temperature probes. All outbreak sequences formed a single genetic cluster within the C. auris South African clade. The sequenced isolates from reusable equipment were genetically related to isolates from the patients. CONCLUSIONS: The transmission of C. auris in this hospital outbreak was found to be linked to reusable axillary temperature probes, indicating that this emerging pathogen can persist in the environment and be transmitted in health care settings. (Funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University and others.).

Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey.

BACKGROUND: Transmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA. METHODS: In this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs). FINDINGS: From May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0-12). INTERPRETATION: Isolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission. FUNDING: US Centers for Disease Control and Prevention.

Infection control measures to prevent hospital transmission of candida.

Invasive candida infections are the most important causes of nosocomial infections in intensive care units and in risky groups such as immunosuppressed patients. These infections lead to undesirable consequences such as increased morbidity and mortality in patients, prolongation of hospital stay, and increased hospital costs. In recent years, the incidence of non-albicans Candida spp.'s has increased. Unfortunately, some of these species are naturally resistant to first-line antifungals. In addition, biofilm formation on the central venous catheter and invasive devices may cause treatment failure. The age of the patients, co-morbid diseases, the units where they are treated, the antibiotics and antifungals that are used for the treatment, and invasive devices are risk factors for invasive candida infections. Some of these risk factors can be reduced by the behavior of health-care workers. The most important goal is to take precautions before the occurrence of invasive candida infections. Infection control measures to prevent hospital transmission of candida are very important. Compliance with hand hygiene before and after contact with the patient is the most important step to prevent the spreading of Candida spp. Observation of maximal barrier precautions during invasive catheterization is another important clause of this aim. Avoiding unnecessary invasive devices, antibiotics, and parenteral nutrition are also important to reduce the colonization of candida.

Candida auris Infection Leading to Nosocomial Transmission, Israel, 2017.

A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogenetic analysis showed resemblance of C. auris to isolates from South Africa but not Israel, suggesting travel-associated infection. C. auris infection occurred weeks later in another patient at the same hospital, suggesting prolonged environmental persistence.