Introduction
Candida auris is an emerging multidrug-resistant yeast that can cause healthcare-associated invasive infections that may be extremely difficult to treat, leading to high mortality. It was first isolated in 2009 in Japan from the ear discharge of a hospitalized patient. Since then, cases of C. auris have been reported in Asia, Africa, the Middle East, Europe, South America, and, recently, North America.[1–10]C. auris is associated with nosocomial outbreaks in intensive care settings, and transmission despite the implementation of enhanced infection prevention and control measures is a particular concern. C. auris can infect people of all ages; however, C. auris candidiasis is most common in older persons. The risk factors associated with invasive C. auris infections also mimic those associated with other Candida species. Reviews of patient cases with C. auris infections revealed that they were often critically ill, had prior antibiotic or antifungal therapy, had the presence of central venous catheters (CVCs), underwent recent surgery, or were immunocompromised.[7,11] There are three distinctive features of C. auris from the analysis of these studies, which have been elucidated. First, most clinical laboratories misidentify this pathogen. Biochemical identification systems that have been used in many clinical laboratories, such as VITEK 2 and API 20C AUX, have apparently misidentified C. auris isolates as C. haemulonii. The second issue is that infections caused by C. auris pose a clinical problem due to the erratic profile of antifungal tolerance, which often follows this organism.[12] For the treatment of invasive Candida infections, there are currently only three types of systemic antifungals available: polyenes, triazoles, and echinocandins. The third feature is that it can be transmitted between patients in health-care settings and cause healthcare-associated outbreaks.[5–7,13]
The most common form of infection is candidemia, with crude mortality of nearly 30%, but up to 70% in some reports.[14] Unlike most other Candida species, which do not require transmission-based precautions, C. auris necessitates the application of particular infection control measures, similar to those used to control MRSA and carbapenem-resistant Enterobacteriaceae.[15] This article depicts the emergence of multidrug-resistant C. auris and controlling its spread by appropriate infection control measures.
Materials and Methods
The study was conducted in the trauma intensive care unit (TICU) of a tertiary care hospital in New Delhi from September 2019 to November 2019. Blood culture samples were obtained from all suspected cases of fungal septicemia as part of the surveillance of device-associated infections. Samples were processed in BacT/Alert automated blood culture system. Positive flagged bottles were further subcultured into blood agar, MacConkey agar, and Sabouraud Dextrose Agar (SDA) with and without cycloheximide and incubated at 37°C. All suspected candida isolates were identified using both conventional methods and VITEK 2 (version 8.01) Biomerieux. Conventional identification was performed by Gram stain, germ tube test, growth on CHROMagar, and by observing the morphology on Corn Meal Agar. C. auris isolates were suspected by pink growth on CHROMagar [Figure 1] which was then subjected to identification on the VITEK 2 system and confirmation by heat test and salt tolerance test. The VITEK 2 YST ID colorimetric cards were used for automated identification. Final identification was done using matrix-assisted laser desorption/ionization–time-of-flight mass spectroscopy (MALDI-TOF), Biotyper OC, version 3.1 (Bruker Daltonics, Bremen, Germany).
;)
Figure 1: Light pink growth of Candida auris on CHROMagar
Results
Out of 24 suspected fungal septicemia cases from trauma ICU (TICU), it was found that three patients had C. auris septicemia. All three isolates were resistant to fluconazole and voriconazole. Before any action was taken by the infection control team, the health-care staff were intimated about the isolation of C. auris, and management for the same was discussed. Due to the relatively low resistance to echinocandins, it was recommended that an echinocandin empirical therapy be initiated in patients having C. auris septicemia. However, all three patients succumbed to death even while on echinocandins. Swabs from different body sites (groin and axilla) were taken as a part of active surveillance and C. auris was isolated from the axilla of the index case, whereas others were negative for the same.
Actions taken
Contact tracing and active surveillance
Subsequent to the isolation of C. auris, active surveillance was undertaken on all patients admitted to ICU where the index case was present. Patients were screened for C. auris colonization at two sites, the axilla and groin. Sterile cotton swabs moistened with sterile normal saline (0.9%) were used to swab sites. Swabs were directly transported to the laboratory in a sterile tube and inoculated onto SDA. Plates were incubated at 37°C for 48 h. All suspected Candida isolates were identified by various conventional techniques as mentioned above and confirmed by MALDI-TOF.
Hand hygiene and contact precautions
Hand hygiene is one of the most basic components of infection control. The working staff were educated on performing adequate hand hygiene, based on the WHO-recommended five moments and six steps of using soap or alcohol hand rub.[16] As part of contact precautions according to the Centers for Disease Control and Prevention (CDC) guidelines, spatial separation of at least 3 feet between patients and the use of privacy curtains to limit direct contact was maintained as a single patient room is a limitation due to lack of infrastructure.[17] Donning personal protective equipment (PPE) upon room entry and properly discarding before exiting the patient room was done to contain pathogens and health-care personnel were advised to wear a gown and gloves for all interactions that may involve contact with the patient or the patient’s environment. Health-care personnel was advised to always wear gloves to reduce hand contamination, avoid touching surfaces outside the immediate patient care environment while wearing gloves, and perform hand hygiene before donning gloves and following glove removal.
Disinfection
Surface cleaning of high-touch surfaces and equipment was carried out with 1% sodium hypochlorite (NaOCl) followed by 70% alcohol. Cleaning and disinfecting environmental surfaces were done on a more frequent schedule.[18]
Other measures
To clean the body surface, sponging with 2% chlorhexidine gluconate (CHG), 0.5% chlorhexidine mouthwash, and chlorhexidine-impregnated pads for CVC exit sites were started for the patients.[19] Prospective surveillance was also carried out for a month until there was no evidence of C. auris transmission.[18] The infection control team conducted intensive training for all staff working in the TICU to emphasize strict infection control practices. The daily CHG washing was carried out under the direct supervision of the infection control nurse. Health-care workers were also educated on measures to be taken to prevent catheter-related bloodstream infections and aseptic blood collection.
Discussion
The inability of C. auris to grow germ tube, pale purple, or pink smooth colonies on CHROMAgar and the ability to grow at 42°C and 10% NaCl when cultured in Sabouraud broth with mannitol, all helped in establishing the identification of the pathogen. C. auris have an exceptional thermoresistance that helps it to grow at temperatures ranging from 30°C to 42°C, but only slowly and weakly at 42°C.[20] This attribute can be used to readily distinguish this pathogen from other species and has been cited as a potential cause for this pathogen‘s high survival in humans.
Out of 24 patients, C. auris accounted for fungal septicemia in three patients. A prospective multicenter study from India reviewing cases of candidemia acquired from an ICU found that C. auris was isolated in 19 out of 27 ICUs, representing 5.2% of cases. However, in the present study, C. auris accounted for 12.5% of candidemia cases in a tertiary care trauma center in Delhi. According to studies, the global prevalence of candidemia has risen fivefold in the past decade, with developing nations seeing much higher rates of candidemia than developed countries.[21,22] In a recent study encompassing 72 ICUs among 14 European countries, Klingspor et al. identified candidemia in surgical patients in ICUs in 9 out of 1000 admissions.[23] The most worrying element of our research was the resistance profile of C. auris to Fluconazole and Voriconazole (FLU and VRC), two of the most extensively utilized “empiric” antifungals in Indian health-care settings in situations of unexplained fever/sepsis where antibacterial alone proves futile. Due to relatively low resistance to echinocandins, patients suspected of having C. auris infections can begin echinocandin empirical therapy before antifungal susceptibility testing of collected strains, and the echinocandins can subsequently be maintained or altered based on the susceptibility results. To reduce the number of deaths caused by C. auris, it is recommended that echinocandin treatment be started as soon as possible.
Recommendations for infection control are the same for a patient infected or colonized with C. auris since both pose a risk for transmission. The four approaches that we applied were: clearance from colonized sites using chlorhexidine body and mouthwashes; elimination from the environment using disinfectants; removal from hands of health-care workers by training; improvements in hand hygiene compliance and training of health-care workers pertaining to strict infection control measures and aseptic sample collection.
To contain the transmission, patients with C. auris should be placed in a single room on contact precautions with dedicated, noncritical equipment but due to lack of infrastructure cohorting of patients can be done by maintaining a spatial separation of at least 3 feet between patients and using PPE appropriately.[17]
Health-care personnel may play a role in transmitting C. auris from one patient to another, particularly with inadequate hand hygiene and contact precautions and through the movement and use of contaminated equipment. In a study of a North Indian tertiary hospital, C. auris was detected on the hands of four health-care workers (2.8%); this was likely due to inadequate hand hygiene as opposed to long-term colonization.[13] Therefore, hand hygiene was strictly reinforced and hand hygiene compliance was also observed among all staff working in TICU.
CHG, a commonly used antiseptic, is the most studied antiseptic against C. auris. It is frequently used in the decolonization of patients as well as added to hand soaps in health-care settings. CHG has been reported to be effective against Candida species in several studies.[24–27] Sherry et al. showed that CHG, at a concentration of <0.02% with a contact time of 24 h, was effective in inhibiting the growth of the planktonic cells and biofilms of clinical isolates of C. auris.[28] In one report, however, the authors indicated that some patients had persistent colonization because they were not able to eliminate colonization of the gut, as the patients had diarrhea.[13] However, in our study, all the patients were found to be free from C. auris colonization after regular washing with 2% CHG, on repeat culture from colonizing sites.
Contaminated environmental surfaces and fomites can transmit C. auris. Surveillance studies have shown that C. auris can be isolated from environmental surfaces in health-care facilities. Experiments have demonstrated that C. auris can persist and be grown for at least 14 days on both damp and dry surfaces.[29] The pathogen’s persistence on surfaces provides possibilities for it to colonize or infect hospitalized patients and health-care personnel. During the first epidemic at a UK hospital, a study was conducted which revealed that the minimum contact time necessary for C. auris acquisition is 4 h.[6] Therefore, disinfection of environmental surfaces plays a key role in inhibiting the spread of C. auris in health-care settings. In the health-care context, chlorine-based disinfectants such as NaOCl and sodium dichloroisocyanurate are also widely employed for disinfection. They are the most studied for disinfection against C. auris because they have been previously shown to be extremely effective against other Candida species. In our study, surface cleaning was performed using 1% NaOCl followed by 70% alcohol. In vitro studies have also confirmed the efficacy of chlorine-based disinfectants. Moore et al. utilized a quantitative suspension test on a number of clinical isolates of C. auris that had been treated with 1000 ppm chlorine to determine the efficacy of a routinely used chlorine-based disinfectant (Haz-Tab).[30] The efficiency of chlorine-based disinfectants has also been demonstrated in vitro investigations. Kean et al. infected cellulose matrix, stainless steel, and polyester with clinical isolates of C. auris and assessed NaOCl at 1000 and 10,000 ppm. NaOCl at contact periods of 5 and 10 min and at all concentrations showed substantial mortality on all substrates.[31] However, of all materials tested, complete eradication was achieved only on cellulose substrates.
With the help of the composite swabbing technique, we could find the exact source of the pathogen. The decolonization and infection control measures undertaken seemed to arrest the spread of C. auris further.
Limitations
Screening of health-care workers for the presence of C. auris colonization and environmental sampling to look for the presence of C. auris was not done which could have further helped us in detecting the carriers of this particular pathogen.
Conclusion
The persistence and recurrence of C. auris in the hospital environment require rigorous decontamination, disinfection, and decolonization protocols to be implemented. Patients with C. auris infections should be kept in separate wards under strict contact precautions as detailed by the CDC and started on empirical echinocandin therapy while awaiting the outcome of the laboratory tests. Admission screening of patients from infected sites or areas, active surveillance to identify carriers, and prompt notification of the clinical infection control team is important and can prevent the transmission of C. auris in hospitals.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, et al. First three reported cases of nosocomial fungemia caused by
Candida auris. J Clin Microbiol 2011;49:3139–42.
2. Chowdhary A, Sharma C, Duggal S, Agarwal K, Prakash A, Singh PK, et al. New clonal strain of
Candida auris, Delhi, India. Emerg Infect Dis 2013;19:1670–3.
3. Magobo RE, Corcoran C, Seetharam S, Govender NP.
Candida auris-associated candidemia, South Africa. Emerg Infect Dis 2014;20:1250–1.
4. Emara M, Ahmad S, Khan Z, Joseph L, Al-Obaid I, Purohit P, et al.
Candida auris candidemia in Kuwait, 2014. Emerg Infect Dis 2015;21:1091–2.
5. Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F, et al. First report of
Candida auris in America:Clinical and microbiological aspects of 18 episodes of candidemia. J Infect 2016;73:369–74.
6. Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, et al. First hospital outbreak of the globally emerging
Candida auris in a European hospital. Antimicrob Resist Infect Control 2016;5:35.
7. Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, et al. Investigation of the first seven reported cases of
Candida auris, a globally emerging invasive, multidrug-resistant fungus –United States, May 2013-August 2016. MMWR Morb Mortal Wkly Rep 2016;65:1234–7.
8. Ben-Ami R, Berman J, Novikov A, Bash E, Shachor-Meyouhas Y, Zakin S, et al. Multidrug-resistant Candida haemulonii and
C.auris, Tel Aviv, Israel. Emerg Infect Dis 2017;23:195–203.
9. Morales-López SE, Parra-Giraldo CM, Ceballos-Garzón A, Martínez HP, Rodríguez GJ, Álvarez-Moreno CA, et al. Invasive infections with multidrug-resistant yeast
Candida auris, Colombia. Emerg Infect Dis 2017;23:162–4.
10. Ruiz Gaitán AC, Moret A, López Hontangas JL, Molina JM, Aleixandre López AI, Cabezas AH, et al. Nosocomial fungemia by
Candida auris:First four reported cases in continental Europe. Rev Iberoam Micol 2017;34:23–7.
11. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et al. Simultaneous emergence of multidrug-resistant
Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 2017;64:134–40.
12. Mizusawa M, Miller H, Green R, Lee R, Durante M, Perkins R, et al. Can multidrug-resistant
Candida auris be reliably identified in clinical microbiology laboratories?. J Clin Microbiol 2017;55:638–40.
13. Biswal M, Rudramurthy SM, Jain N, Shamanth AS, Sharma D, Jain K, et al. Controlling a possible outbreak of
Candida auris infection:Lessons learnt from multiple interventions. J Hosp Infect 2017;97:363–70.
14. Osei Sekyere J.
Candida auris:A systematic review and meta-analysis of current updates on an emerging multidrug-resistant pathogen. Microbiologyopen 2018;7:e00578.
15. Forsberg K, Woodworth K, Walters M, Berkow EL, Jackson B, Chiller T, et al.
Candida auris:The recent emergence of a multidrug-resistant fungal pathogen. Med Mycol 2019;57:1–12.
17. Centers for Disease Control and Prevention, Precautions to Prevent Transmission of Infectious Agents. Available from:
https://www.cdc.gov/infectioncontrol/guidelines/isolation/precautions.html. [Last accessed on 2022 Jun 17].
18. Centers for Disease Control and Prevention, Infection Prevention and Control for Candida auris. Available from:
https://www.cdc.gov/fungal/candida-auris/c-auris-infection-control.html#transmission. [Last accessed on 2022 Jun 17].
19. Indian Council of Medical Research, Candida auris in Healthcare Settings. Available from:
https://main.icmr.nic.in/sites/default/files/guidelines/candida_Auris.pdf. [Last accessed on 2022 Jun 17].
20. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 2009;53:41–4.
21. Barchiesi F, Orsetti E, Gesuita R, Skrami E, Manso E Candidemia Study Group. Epidemiology, clinical characteristics, and outcome of candidemia in a tertiary referral center in Italy from to 2014. Infection 2016;44:205–13.
22. Chakrabarti A. Fungal Infections in Asia: The Eastern Frontier of Mycology. 1st ed. Gurgaon, India: Elsevier; 2013.
23. Klingspor L, Tortorano AM, Peman J, Willinger B, Hamal P, Sendid B, et al. Invasive candida infections in surgical patients in intensive care units:A prospective, multicentre survey initiated by the European confederation of medical mycology (ECMM) (|y2006-2008). Clin Microbiol Infect 2015;21:87.e1–87.e10.
24. Fathilah AR, Himratul-Aznita WH, Fatheen AR, Suriani KR. The antifungal properties of chlorhexidine digluconate and cetylpyrinidinium chloride on oral Candida. J Dent 2012;40:609–15.
25. Salim N, Moore C, Silikas N, Satterthwaite J, Rautemaa R. Chlorhexidine is a highly effective topical broad-spectrum agent against Candida spp. Int J Antimicrob Agents 2013;41:65–9.
26. Yildirim M, Sahin I, Oksuz S, Sencan I, Kucukbayrak A, Cakir S, et al. Hand carriage of Candida occurs at lesser rates in hospital personnel who use antimicrobial hand disinfectant. Scand J Infect Dis 2014;46:633–6.
27. Mozayeni MA, Hadian A, Bakhshaei P, Dianat O. Comparison of antifungal activity of 2% chlorhexidine, calcium hydroxide, and Nanosilver gels against candida albicans. J Dent (Tehran) 2015;12:109–17.
28. Sherry L, Ramage G, Kean R, Borman A, Johnson EM, Richardson MD, et al. Biofilm-forming capability of highly virulent, multidrug-resistant
Candida auris. Emerg Infect Dis 2017;23:328–31.
29. Piedrahita CT, Cadnum JL, Jencson AL, Shaikh AA, Ghannoum MA, Donskey CJ. Environmental surfaces in healthcare facilities are a potential source for transmission of
Candida auris and other candida species. Infect Control Hosp Epidemiol 2017;38:1107–9.
30. Moore G, Schelenz S, Borman AM, Johnson EM, Brown CS. Yeasticidal activity of chemical disinfectants and antiseptics against
Candida auris. J Hosp Infect 2017;97:371–5.
31. Kean R, Sherry L, Townsend E, McKloud E, Short B, Akinbobola A, et al. Surface disinfection challenges for
Candida auris:An
in-vitro study. J Hosp Infect 2018;98:433–6.
