Assessment of environmental and occupational exposure while working with multidrug resistant (MDR) fungus Candida auris in an animal facility

Abstract

In less than a decade since its identification in 2009, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality. Unlike any other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models use inoculums as high as 10 7 -10 8 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. Using real-time quantitative PCR and culture, we monitored the animal holding room as well as the procedure room for up to six months while working with an intravenous model of C. auris infection. This study determined that shedding of the organism is dose-dependent, as detectable levels of C. auris were detected in the cage bedding when mice were infected with 10 7 and 10 8 cells, but not with doses of 10 5 and 10 6 cells. Autoclaving bedding in closed microisolator cages was found to be an effective way to minimize exposure to animal caretakers. We found that tissue necropsies of infected mice were also an important source of potential source exposure to C. auris. To mitigate these potential exposures, we implemented a rigorous "buddy system" workflow and a disinfection protocol that uses 10% bleach followed by 70% ethanol and can be used in any animal facility when using small animal models of C. auris infection.reported to be as high as 256 mg/L for fluconazole and > 2 mg/L for amphotericin B. (1)(2)(3)(4)(5) The Centers for Disease Control (CDC) has documented that C. auris behaves more like transmissible bacterial multidrug resistant organisms (MDROs) such as methicillin resistant Staphylococcus aureus (MRSA) than any other Candida species. (6) Of particular concern is that the unpredictable antifungal resistance profile of C. auris is also showing evidence of reduced susceptibility to the echinocandins, a third class of antifungals. ( 4) C. auris causes invasive bloodstream infections with reported mortality rates as high as 30-60% in Venezuela and India, and most recently, a reported mortality rate of up to 78% in Panama. (7)(8)(9) Although the origin of C. auris is unknown, infections with this organism have been documented on five continents in at least 18 countries, including the United States. (7,8,(10)(11)(12)(13)(14)(15)(16)(17)(18) C. auris has a predilection for the skin, making transmission and colonization from person to person quite easy (6) . C. auris has been found to be alarmingly persistent in the environment, and has been reported in hospital and nursing home settings. (19,20) A recent study at the Louis Stokes Veterans Affairs Medical Center in Cleveland, Ohio found that C. auris exhibits a greater propensity to persist for up to 7 days on surfaces than any other Candida species. Surfaces that tested positive included moist surfaces, such as hospital...

Multidrug Resistance in Mammals and Fungi—From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms

“…For example, C. auris is a newly emerging pan-resistant fungal pathogen first reported from an ear infection in Japan in 2009 [ 232 ]. Within a decade, C. auris appeared in more than 40 countries around the globe, causing hospital outbreaks of invasive candidemia [ 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 ]. Importantly, C. auris is also causing severe superinfections with viruses, as seen in a recent co-infection of COVID-19 patients in a Mexican hospital ICU, leading to a dramatic overall mortality of 83%.…”

Candida auris is rendered non-viable by medium-chain fatty acids

“…causing hospital outbreaks with high mortality rates. Factors contributing to its virulence likely include C. auris' persistence both as a skin colonizer and in the environment (1,2); its ability to transfer to other patients or healthcare workers; and its resistance to various disinfection measures and antifungal drugs [reviewed in (3,4)].…”

“…To work with the strains of C. auris, precautions were taken as previously described (2). The susceptibility of the C. auris strains to octanoic and decanoic acids was determined using a broth microdilution assay [(12) and supplemental methods].…”