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Candida auris is emerging as a prevalent urinary pathogen [1]

['Alyssa Ann La Bella', 'Department Of Biological Sciences', 'University Of Notre Dame', 'Notre Dame', 'Indiana', 'United States Of America', 'Felipe Hiram Santiago-Tirado', 'Ana Lidia Flores-Mireles']

Date: 2025-05 

Urinary tract infections (UTIs) are one of the most common infections, with a subgroup of these infections, catheter-associated UTIs (CAUTIs), accounting for 40% of nosocomial infections. While the majority of CAUTI pathogens are bacterial, the second most common pathogen is the fungus Candida albicans. However, in recent years, Candida auris has increasingly been isolated from urine, indicating C. auris’ potential as a urinary pathogen. C. auris has rapidly emerged as a human pathogen worldwide, becoming a serious health threat. This is of great concern due to its antifungal resistance, adherence to inanimate surfaces, high mortality rates, and the extensive knowledge gap regarding C. auris’ prevalence and pathophysiology. To understand whether C. auris is prevalent in the urinary tract, we analyzed 12,996 C. auris clinical strains and their frequency related to urine and urinary catheters. We identified urine as the second most common C. auris isolation source in the United States and the third most common worldwide. Anecdotally, C. auris urine isolates are often associated with urinary catheters and high mortality rates. Furthermore, there has been an early indication of urinary isolates developing echinocandin resistance. With the increasing incidence of uropathogenic C. auris, it is critical to have an in-depth understanding of C. auris pathogenesis in the urinary tract to effectively prevent and treat these infections.

Funding: This work was done in the Flores-Mireles Laboratory by the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK128805 (to A.L.F.M. and A. A.L.), R01AI177875 and R21AI71742 (to F.H.S-T); Good Venture Foundation (Open Philanthropy) grant (to A.L.F.M., and A.A.L.); the Arthur J. Schmitt Leadership Fellowship (to A. A. L.); and the Eck Institute for Global Health Fellowship at the University of Notre Dame (to A. A. L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2025 La Bella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Candida auris was an environmental fungus until 2009, when it was isolated from an ear infection in Japan [1]. Following that, C. auris was recognized as a common cause of severe infection with high mortality in healthcare settings throughout the world [1]. C. auris’ success is attributed to its multi-antifungal resistance and biofilm formation, aggregation, immune evasion, and thermotolerance, allowing it to survive on inanimate surfaces as well as in human hosts [1]. While the ear canal was the first patient isolation source, C. auris has been isolated from other body sites, including axilla, urine, bloodstream, and skin.

Notably, urine has become a predominant C. auris isolation source in patients, emerging as a urinary pathogen (uropathogen) [2]. Urinary tract infections (UTIs) are common infections classified as uncomplicated or complicated [3]. Uncomplicated UTIs (uUTIs) occur in healthy individuals without pre-existing conditions by uropathogenic Escherichia coli [3]. Conversely, complicated UTIs (cUTIs) are associated with urinary obstruction/structural abnormality, a compromised urinary tract, or underlying medical conditions. Examples include patients with urinary catheters, kidney stones, renal failure, transplantation, and obstructions [3].

Despite its benefits, urinary catheterization renders patients susceptible to catheter-associated UTIs (CAUTIs), accounting for 80% of cUTIs and ~ 40% of all hospital-acquired infections [4]. Unlike uUTIs, CAUTIs are not gender or age-specific and are caused by both bacteria and fungi [3]. It is estimated that ~15–25% of hospitalized patients require a urinary catheter, with use increasing to 60% in intensive care unit (ICU) patients [5]. In nursing homes, ~ 7% of residents worldwide [6] and ~ 11.9% of residents in the United States (US) utilize catheters [7], and ~ 50% will experience symptomatic CAUTIs [8]. Persistent CAUTIs often lead to urosepsis, septicemia, and death [3]. Importantly, recent clinical studies indicate that CAUTI is an independent and significant risk factor for ICU mortality [9].

Recently, Candida species, specifically C. albicans, have increased their prevalence in the urinary tract, accounting for 17.8% of CAUTIs [3]. Yet fungal CAUTIs remain understudied compared to its bacterial counterparts [3,10]. Alarmingly, 25% of sepsis cases are from urinary isolates [11]; thus, understanding fungal infections is critical to reduce patient urosepsis, candidemia, and mortality [12].

Importantly, with C. auris outbreaks in healthcare facilities and fungal UTI/CAUTI increase, it is essential to investigate C. auris as a uropathogen. Here, we analyze C. auris clinical data in relation to the urine environment and as a uropathogen.

Urinary isolates: uUTI or CAUTI? Often, when the isolation source was listed as “urine”, it remained unspecified whether patients had an indwelling urinary catheter, making it difficult to associate C. auris with uUTI or CAUTIs. To understand if C. auris urine isolates coincide with urinary catheter usage, we examined five case studies that provided additional patient details: A 2024 study from rural West India found that >60% (6/9) of C. auris cases were urinary isolates. Of those six patients, five isolates came from urine while one was isolated from a urinary catheter. Furthermore, all five patients with a urine isolate had an indwelling catheter. Five patients died and one patient left against medical advice [13]. A 2024 study from a Bahrain tertiary care hospital analyzed 59 patient samples with C. auris invasive infection or colonization. The most prevalent isolation sources were groin, with 20 samples (33.9%), and urine, with 15 samples (25.4%). Twenty-three patients had a urinary catheter (44.2%); although it is unknown whether they had a corresponding urine isolate. Twenty-six patients died (44.1%), wherefrom seven patients (26.9%) had urine isolates [14]. A 2023 study in Brazil found that 2 of 11 C. auris isolates originated from urine. Both patients had an indwelling urinary catheter and succumbed to their illnesses [15]. In a 2023 Saudi Arabia study, C. auris was isolated from 53 patients, with 16 isolates from urine (30.2%). Of the 53 patients, 17 (32.1%) had an indwelling medical device; however, which patients and the medical device type were not detailed [16]. During a 2020 COVID-19 outbreak in a Lebanese tertiary care facility, 14 C. auris cases were documented. Ten samples came from the respiratory tract (71.4%) and three from urine (21.4%). Two patients with urinary isolates had indwelling urinary catheters. The urinary isolate patient without the urinary catheter died of septic shock [17]. While we cannot directly associate C. auris urine isolates with urinary catheter usage, the anecdotal evidence from the case reports suggests that these isolates frequently coincide with urinary catheters. Studies that identify/correlate positive urine samples with urinary catheter presence are needed to understand if C. auris causes CAUTIs, uUTIs, or both.

Are C. auris uropathogens developing multidrug resistance? An important trend regarding urinary isolate-antifungal resistance is noted. While most C. auris isolates have developed resistance to azoles, C. auris echinocandin (caspofungin, micafungin, and anidulafungin) resistance is less frequent [1]. While datasets on multidrug resistance for specific isolation sources are not currently compiled or available, several studies have found echinocandin resistance in C. auris urine isolates. A study described that a patient had C. auris isolates from trachea secretion and urine. The trachea isolate remained echinocandin-susceptible, but the urinary isolate developed resistance [18]. A 2018–2019 study in Kuwait identified three C. auris urinary isolates with reduced echinocandin susceptibility [19]. A 2018–2021 United Arab Emirates study found urinary isolates had the highest echinocandin resistance, with 9.3% and 4.2% developing resistance to caspofungin and micafungin, respectively [20]. Finally, a US case study showed a 54-year-old male with an indwelling urinary catheter developed echinocandin-resistant candidemia after several positive C. auris urine cultures [21]. The fact that C. auris urine isolates exhibited higher echinocandin resistance is unsurprising since the majority of uropathogens are developing multi-drug resistance [3]. Multi-drug resistance can be attributed to biofilm formation but also could be related to antimicrobial concentration in the bladder, which is affected by constant urine accumulation and voiding. Effective treatment of urinary infections with echinocandins is challenged by their limited urinary tract concentrations, despite higher levels in blood and sputum [22]. Suboptimal echinocandin concentrations during repeated treatment of urinary C. auris infections could drive the evolution of resistance in urinary isolates [22,23]. While echinocandins remain effective against C. auris isolates from ear [24] and bloodstream [25] infections, urinary isolates exhibit altered antifungal susceptibility [18–21]. These findings warrant future studies about C. auris urine isolates and their ability to develop resistance to these last resort antifungals.

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[1] Url: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013138

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