Does Candida auris colonize the oral cavity? A retrospective institutional experience

Candida auris (C. auris) was first isolated in 2009 from an ear canal infection in a patient in Japan (Satoh et al., 2009) and since then, the scientific community has witnessed an exponential emergence of outbreaks in healthcare facilities world-wide, with overall mortality rates ranging from 30-60% (Alvarez-Moreno et al., 2023; Egger et al., 2022). In contrast to other Candida species, C. auris persistently colonizes the skin and nosocomial surfaces, and demonstrates the capacity to resist common disinfectants and to spread rapidly among patients (Kordalewska & Perlin, 2019; Welsh et al., 2017). Most concerning, C. auris exhibits a high level of resistance to multiple drug classes and misidentification by available commercial laboratory studies has complicated its clinical management (Kordalewska & Perlin, 2019).

C. auris was first reported in the United States in 2016 and has been spreading at an alarming rate since. Due to its transmissibility and high levels of antifungal resistance, C. auris has been categorized as a public health threat by the World Health Organization and is currently among the 4 most critical fungal pathogens (including Cryptococcus neoformans, Aspergillus fumigatus, and C. albicans) (WHO, 2022). Beginning in 2018, C. auris has been mandated to be reported in the United States (CSTE, 2018). To date, C. auris isolates have been recovered from several head and neck mucosal sites (ocular, nasal, pharynx, tracheal), as summarized in Table 1, as well as blood, sputum, pus, urine, skin, abdominal and pleural fluid, and other mucosa (rectal, vulvovaginal, urinary tract) (Khan et al., 2018; Nobrega de Almeida et al., 2021; Piatti et al., 2022; Zhang et al., 2022). Although C. auris has not been reported to colonize oral mucosal surfaces, it is not clear whether its presence was actively screened for in the oral cavity. Herein, we report the results of a 2-year retrospective institutional experience that attempts to determine whether C. auris is a commensal colonizer of the oral cavity.

TABLE 1.

HEAD AND NECK MUCOSAL SITES ASSOCIATED WITH CANDIDA AURIS.

# of positive cases/total	Country	Patient gender	Positive mucosal sites	Comorbidity	Culture media	Deaths	References (Authors/year)
1/1258	UK	1/NS	Nose	NS	CHROMagar	NS	Schelenz et al., 2016
1/3	Columbia	1M	Eye	Cutaneous T-cell Hodgkin lymphoma	Sabouraud’s dextrose agar, CHROMagar	1*	Parra-Giraldo et al., 2018
≥ 21**	Kuwait	NS	Tracheal aspirate, eye, nose	“Life-threatening conditions”	CHROMagar Candida	NS	Khan et al., 2018
1	USA (NY)	1M	Eye	HIV infection, syphilis	NS	0	Shenoy et al., 2019
1	USA (NY)	1M	Eye	HIV infection	NS	0	Breazzano et al., 2020
1/1414	USA (IL)	1/NS	Nose	NS	Mold agar	NS	Malczynski et al., 2020
1	Spain	1M	Pharynx	None	CHROMagar	1***	Mirabet et al., 2021
3/46	Brazil	3/NS	Nose	Covid-19 infection	CHROMagar	NS	Nobrega de Almeida et al., 2021

^*Cause of death attributed to metastatic disease.

^**Some patients had >1 isolate-positive site.

^***Cause of death attributed to brain trauma from motor vehicle accident.

NS, not stated

A single-center retrospective institutional experience from 5/2021 to 5/2023 was performed from saliva samples obtained from patients with clinical evidence of oral candidiasis or from patients with symptoms of oral burning, suggestive of subclinical disease who underwent fungal culturing for confirmation as part of their standard of care diagnosis. A total of 310 saliva samples were obtained from patients attending the Oral Medicine Clinic at the University of Maryland School of Dentistry. Samples were cultured on the fungal selective agar media yeast extract peptone dextrose and the chromogenic media CHROMagar^™ Candida Plus was utilized for speciation, based on colony color and morphology.

Culture results indicated 222/310 (71.6%) samples were negative for Candida growth and 88 (28.4%) were positive. Among the positive cultures, C. albicans was the most predominately isolated species, noted in 97.7% (86/88) of cultures, whereas only 2.3% (2/88) were solely positive for C. tropicalis and 1.1% (1/88) for C. glabrata (mixed with C. albicans). C. auris was not recovered from any of the samples collected during this 2-year period.

To our knowledge, this is the first retrospective study to screen for the presence of C. auris in the oral cavity conducted in a large cohort of subjects using commercially available culture methods. The novel chromogenic medium CHROMagar^™ Candida Plus used here has been shown to provide a reliable and rapid presumptive identification of C. auris and therefore, constitutes a valuable tool in surveillance efforts to screen for C. auris in healthcare settings (Marathe et al., 2022)

Interestingly, Vila et al explored the pathogenesis of C. auris in different in vivo and ex vivo models and was able to show that C. auris avidly adhered to intravascular catheters implanted in mice and to tongue tissue ex vivo. Importantly and for the first time, it was reported that these same isolates failed to colonize and persist in the oral cavity in a mouse model of oral candidiasis (as demonstrated by microbial recovery and tissue histopathology analysis) (Vila et al., 2020). These in vivo findings established the affinity for C. auris to adhere to abiotic surfaces, such as catheters and other implanted medical devices (the main cause for development of bloodstream and systemic infections), and mitigated any significant bioadaptive colonization potential involving oral mucosa. Moreover, a recent in vitro study found C. auris to be highly susceptible to killing by the host-produced salivary antimicrobial peptide histatin-5, which plays a pivotal role in innate immunity (Pathirana et al., 2018).

It is well established that critically ill hospitalized patients are at risk of developing systemic Candida infection with high morbidity and mortality, particularly immunocompromised and immunosenescent individuals (Qiao et al., 2023). Despite the lack of C. auris recovery from the oral cavity in our study, it is advocated that hospitals establish surveillance protocols that include testing of oral samples, in addition to the currently implemented screening for skin colonization. Given the risk for person-to-person transmission or autoinoculation, it is important to remain vigilant for the detection of oral mucosal colonization of C. auris, which could potentially lead to the development of systemic disease via the oropharyngeal gateway.

In conclusion, based on this single-center retrospective institutional experience and the C. auris in vivo mouse model of oral candidiasis conducted by Vila et al., C. auris fails to colonize oral mucosal surfaces; however, larger prospective surveillance studies are warranted to confirm these findings (Vila et al., 2020).