Should all hospitalised patients colonised with Candida auris be considered for isolation?

Candida auris is an emerging pathogenic yeast causing nosocomial infections coupled with high mortality mainly in fragile people. It is considered a serious global health threat and classified as critical fungal pathogen on the World Health Organization (WHO) fungal priority pathogens list and listed on the WHO Global research agenda for antimicrobial resistance [1,2]. The organism's implications for patients and healthcare systems are high because of its potential for rapid resistance development and transmission within and between healthcare settings. The latter is furthered by the fact that C. auris is difficult to detect under routine laboratory conditions. In addition, decolonisation of patients is challenging and mortality rates in those infected are high [3,4].

In this issue of Eurosurveillance, Meletiadis et al. [5] describe the prolonged occurrence of Candida auris in a tertiary care hospital in Greece, leading to recurrent waves with increased numbers of colonised patients, followed by increased morbidity due to bloodstream infections. Not only did authors confirm clonality of the involved isolates, but they also demonstrated the emergence of echinocandin resistance over time. Noting how the lack of strict and continuous implementation of infection prevention and control (IPC) measures affected the course of the outbreak, Meletiadis et al. stress the need to implement stringent IPC measures immediately during first detection/introduction of C. auris and underscore the importance of adequate diagnostics and surveillance. This is of utmost importance for preventing and controlling the spread of C. auris and other multidrug-resistant organisms (MDRO) within and between hospitals.

In the Netherlands, a revised national MDRO guideline was published on 11 October 2024 [6]. This version by the Dutch Collaborative Partnership for Infection Prevention Guidelines (SRI, https://www.sri-richtlijnen.nl) includes C. auris for which it was decided that it is justified to isolate all hospitalised patients colonised with C. auris using stringent IPC measures. This decision followed an elaborate discussion, whether or not it is justified to handle patients with resistant and susceptible isolates of C. auris in the same way.

The Dutch hospital setting is renowned for its robust and successful IPC approach. Combined with the national antimicrobial stewardship programme, it has kept the country’s antimicrobial resistance rates at one of the lowest levels in Europe [7]. One outstanding example of this IPC approach is the early adaptation in 1986 of the ‘search and destroy’ strategy to control meticillin-resistant Staphylococcus aureus (MRSA) [8]. A comparable ‘search and contain’ strategy was nationally implemented in 2012, targeting other MDROs, including carbapenem-resistant Enterobacterales, which were emerging in the Netherlands at the time [9]. Currently, the prevalence for MRSA and carbapenem-resistant Klebsiella pneumonia are among the lowest in Europe, at 1.8% and 0.4%, respectively [7].

The first Dutch guideline for MDRO was published in 2005, with the latest revision initiated by the SRI in 2022 [6]. During the concept and revision phase of this guideline, far-reaching IPC measures were initially advised for patients harbouring resistant and susceptible C. auris isolates [10], leading to the above-mentioned discussion among experts whether susceptible isolates of C. auris warrant isolation measures to the same extent as resistant ones. Opponents argued that by definition, a susceptible isolate is not multidrug resistant and therefore should not be treated equally to the resistant variant. Consequently, they suggested less stringent measures for patients colonised or infected with susceptible isolates of C. auris, an approach in line with current practice for resistant Enterobacterales and their susceptible counterparts.

However, following the considerations elaborated further on, members of the MDRO working group reached the final consensus to handle all C. auris isolates equally. Consequently, all patients colonised or infected with C. auris, independent of their susceptibility testing outcome, will be cared for in a single-bed isolation room with an anteroom and adequate ventilation for source isolation. Although an isolation room may seem an excessive measure given the contact-based transmission route of C. auris, it was chosen to enhance compliance with the IPC measures by creating extra attention. The guideline advises gown, gloves and masks for all healthcare workers entering the room and stress the need for thorough room cleaning and adequate hand disinfection.

Considering the experiences and observations by Meletiadis et al., the decision to align the prevention of C. auris transmission regardless of its antifungal resistance will aid to avert C. auris outbreaks and the pathogen from becoming endemic in Dutch hospitals. The following reasoning for the Dutch decision may inform decision-making by others who are facing similar considerations.

Candida auris has demonstrated a notable propensity for rapid resistance development and is the first Candida species to have acquired pan-drug resistance [11]. Even during short term echinocandin treatment, the first-line treatment for systemic C. auris infections, resistance development has been demonstrated during the outbreak described by Meletiadis et al. [5] and unequivocally proven in a patient using whole genome sequencing [12]. For azoles and other antifungal drugs, resistance can arise via multiple mechanisms, including acquired (point) mutations and the upregulation of resistance genes [13,14]. Consequently, patients colonised with initially susceptible strains could harbour or develop resistance during treatment, underscoring the necessity of rigorous infection control measures.

Well-known for its capacity to spread within healthcare settings, C. auris has often led to outbreaks that are challenging to contain [3,5]. Standard cleaning protocols typically used for bacterial MDROs have proven inadequate for eradicating C. auris from the healthcare environment [15]. Its combined properties, such as biofilm formation and salt- and thermotolerance, facilitate prolonged patient colonisation and survival outside the host resembling the outbreak potential of C. parapsilosis, another globally impactful yeast [16,17]. Patients colonised with C. auris serve as reservoirs for transmission to other patients and healthcare workers [18]. Notably, pan-susceptible isolates have led to a multicenter outbreak in Brazil, demonstrating how its pathogenicity and outbreak potential is not solely driven by its antifungal resistance [19]. Isolating all patients, irrespective of the antifungal susceptibility pattern of the colonising isolate, will significantly reduce the risk of transmission within healthcare facilities, thereby averting outbreaks.

Candida auris is challenging to detect accurately using conventional diagnostic methods on samples from routinely screened patient body sites, which may result in underestimation of colonisation rates and delayed implementation of IPC measures [18,20]. Therefore, additional axilla and groin swabs along with qPCR testing are recommended, although PCR-positive samples have proven difficult to culture [20,21]. Fortunately, the recent identification of novel genetic variants (clades) has not impeded molecular detection thus far [11,22,23]. However, decolonisation strategies for patients with C. auris have been largely ineffective, further emphasising the importance of preventive measures, such as isolation, to restrict the healthcare-associated spread of this yeast, particularly in non-endemic areas [4,24].

Invasive infections caused by C. auris and other emerging Candida species, are associated with even higher mortality rates (exceeding 46 %) than the most commonly encountered Candida species in invasive disease, particularly among vulnerable patient populations [25,26]. A survey from 2022 on reported cases of Candida auris infection or carriage, including hospital outbreaks, has demonstrated invasive infections in over 10 % of colonised patients in the European setting [27], and colonisation has occurred within as little as 4 hours of contact [28]. Therefore, preventing the spread of colonisation, even if the strain is initially susceptible to treatment, is crucial to safeguard patient health and minimise the risk of invasive infections.

Adopting a proactive approach by isolating all colonised patients aligns with the principles of infection prevention and control. By implementing comprehensive isolation measures across healthcare settings, facilities can effectively contain the spread of C. auris and mitigate associated risks, including treatment resistance and healthcare-associated infections. With regards to financial impact, preventing a prolonged outbreak lasting over 10 months, and involving 36 patients who became colonised at the hospital including eight with BSI in a tertiary care center in London in 2016, would have saved an estimated 1 million GBP (1.2 million EUR) [29].

Even within yeasts, C. auris is in a league of its own. Prioritising patient safety through comprehensive infection prevention and control measures enables healthcare facilities to manage the risks associated with C. auris colonisation, thereby minimising the likelihood of outbreaks and invasive infections. While C. auris imported cases and outbreaks are increasing in Europe [27], no C. auris outbreaks have been reported in the Netherlands to date, although importations in the Netherlands are gradually increasing [20]. Aside from encouraging stringent IPC in Dutch policymaking, the Dutch National Reference Center for Mycology has requested that all laboratories submit isolates for antifungal susceptibility testing and genotyping to monitor transmission. Continued surveillance for fungal pathogens remains key. Other countries may consider similar approaches and endorse experts to share lessons learned in containing the spread of C. auris.

Note

Eelco Meijer is the head of the Dutch National Reference Center for Mycology, location Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. He partakes in (inter)national discussions and guidelines on Candida auris and is project leader of the ZonMw Consortium CAUTION: Candida auris screening, surveillance and infection control project No:10150022310025.

Andreas Voss is Chair of the Dutch Collaborative Partnership for Infection Prevention Guidelines (SRI), which published the Dutch MDRO guideline in October 2024.