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Candida auris: a global fungal public health threat

Candida auris is an emerging fungal pathogen that has become a world-wide public health threat. While there have been numerous studies into the nature, composition and structure of the cell wall of Candida albicans and other Candida species, much less is known about the C. auris cell wall. We have shown that C. auris cell wall mannan contains a unique phosphomannan structure which distinguishes C. auris mannan from the mannans found in other fungal species. Specifically, C. auris exhibits two unique acid-labile mannose α-1-phosphate (Manα1PO₄) sidechains that are absent in other fungal mannans and fungal pathogens. This unique mannan structural feature presents an opportunity for the development of vaccines, therapeutics, diagnostic tools and/or research reagents that target C. auris. Herein, we describe the successful synthesis and structural characterization of a Manα1PO₄-containing disaccharide moiety that mimics the phosphomannan found in C. auris. Additionally, we present evidence that the synthetic Manα1PO₄ glycomimetic is specifically recognized and bound by cell surface pattern recognition receptors, i.e. rhDectin-2, rhMannose receptor and rhMincle, that are known to play important roles in the innate immune response to C. auris as well as other fungal pathogens. The synthesis of the Manα1PO₄ glycomimetic may represent an important starting point in the development of vaccines, therapeutics, diagnostics and research reagents which target a number of C. auris clinical strains. In addition, these data provide new insights and understanding into the structural biology of this unique fungal pathogen.

Serum (1,3)-beta-d-glucan (BDG) assay is a non–culture-based test recommended for the diagnosis of invasive candidiasis owing to its faster results and higher sensitivity than blood cultures. Its performance might vary for different Candida species. The aim of this study was to determine in vitro levels of BDG in Candida auris culture supernatants and evaluate BDG levels in patients with C. auris candidemia sustained by these stains.

C. auris strains were collected from blood cultures of patients who had a concomitant (–24 to +72 hours) serum BDG test (Fungitell assay). Supernatants of broth media culture of C. auris strains and two Candida albicans (controls) strains were prepared and tested for BDG.

Ten C auris strains were included. Supernatants of two C. albicans considered as controls had a mean BDG level of 1155 pg/mL (considered 100% reactivity). The median BDG level in supernatants of C. auris strains was 275 pg/mL (IQR 165–523 pg/mL), with a median reactivity of 24% (range 6%–72%). In vivo, the median BDG level was 129 pg/mL (IQR, 28–199 pg/mL). Sensitivity of BDG for C. auris candidemia was 60%. All patients received antifungal treatment with an echinocandin initiated a median of 2 days (IQR –8 to 0) before blood collection for BDG.

Our C. auris strains released lower amounts of BDG when compared to C. albicans. Clinical implications include lower sensitivity of serum BDG for the diagnosis of C. auris candidemia with a consequent impact on management protocols in settings with high prevalence of this species.

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain.

The World Health Organization and Centers for Disease Control and Prevention consider the global increase in multidrug‐resistant organisms (MDROs) to be one of the greatest modern threats to public health. Limited treatment options exist for microorganisms such as carbapenem‐resistant Enterobacterales and Candida auris; as a result, infected patients may experience poor outcomes. Perioperative nurses should use infection prevention measures (eg, contact precautions) to prevent the spread of emerging MDROs when transporting patients to and from procedures, caring for patients during procedures, and completing between‐procedure cleaning. Because nurses are involved with all phases of perioperative care, they are well‐positioned to serve as infection prevention champions and provide education to personnel, patients, and caregivers. This article describes actions and steps the perioperative nurse should take during implementation of contact precautions to prevent the transmission of MDROs—specifically, emerging pathogens carbapenem‐resistant Enterobacterales and C auris.