Multidrug-Resistant Candida auris Infections in Critically Ill Coronavirus Disease Patients, India, April–July 2020

In New Delhi, India, candidemia affected 15 critically ill coronavirus disease patients admitted to an intensive care unit during April–July 2020. Candida auris accounted for two thirds of cases; case-fatality rate was high (60%). Hospital-acquired C. auris infections in coronavirus disease patients may lead to adverse outcomes and additional strain on healthcare resources.

T he ongoing coronavirus disease  pandemic has overwhelmed healthcare systems worldwide. Reports from China and New York have highlighted the concern for nosocomial infections, primarily bacterial, in critically ill COVID-19 patients (1)(2)(3). Secondary Candida spp. bloodstream infections in COVID-19 patients with prolonged intensive care unit (ICU) stays have not been documented. However, a new concern coinciding with the brisk expansion of critical care facilities for COVID-19 patients is the potential for nosocomial spread of Candida auris infections (4). C. auris is a global health threat because of its ability to colonize skin, persist in environments, cause nosocomial outbreaks, and lead to severe disease with high mortality rates (5,6).

The Study
Following up on our prediction (4), we report bloodstream infections caused by multidrug resistant C. auris in 1 COVID-19 ICU in New Delhi, India. A total of 596 patients with confirmed COVID were admitted to the 65-bed ICU during April-July 2020. Of these, 420 patients required mechanical ventilation. Overall, candidemia was detected in 15 (2.5%) of the 596 ICU patients; the predominant agent was C. auris for 10 (67%) of those patients. For the remaining 5 patients, candidemia was caused by C. albicans (n = 3), C. tropicalis (n = 1), and C. krusei (n = 1).
We abstracted the following data for the candidemia patients: baseline demographics, medical history, laboratory parameters, microbiological findings, concomitant antimicrobial drug use, and treatments. Isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper, https://www.bruker.com). In addition, species identification was conducted by amplification and sequencing of the internal transcribed spacer region of ribosomal DNA and of the D1/D2 domain of the large subunit ribosomal DNA. Antifungal susceptibility testing was performed by using the Clinical and Laboratory Standards Institute brothmicrodilution method M27-A3/S4 (7). Antifungals tested were fluconazole, voriconazole, posaconazole, isavuconazole, 5-flucytosine, caspofungin, micafungin, anidulafungin, and amphotericin B.

Conclusions
Our findings highlight the role of hospital-acquired C. auris bloodstream infections; the patients were probably infected while hospitalized. C. auris can be transmitted in healthcare settings just like other multidrug-resistant organisms, such as carbapenemresistant Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (4). For 4 of 10 patients studied, bacteremia caused by Enterobacter cloacae and Staphylococcus haemolyticus was also noted. In patients with severe COVID-19, the rate of secondary infections was substantially higher, as has been reported by Goyal  Among fungal co-infections in France, the incidence of putative invasive pulmonary aspergillosis was high (30%) (9).
Several major outbreaks of bloodstream infections caused by C. auris have been reported in India, the United Kingdom, Colombia, South Africa, and the United States (5,(10)(11)(12). In our report, all patients in the ICU had indwelling invasive devices such as central venous and urinary catheters, which may be the source of C. auris infections (i.e., candidemia and urinary tract infection). We anticipate that transmission of C. auris to COVID-19 patients by healthcare personnel is unlikely because of the use of personal protective equipment. However, incorrect and extended use of personal protective equipment can lead to self-contamination and transmission.
Of note, 6 of the 10 patients died, possibly because of multiple underlying health conditions. However, 67% of those who died had persistent candidemia, which may have contributed to their death. Furthermore, multidrug-resistant C. auris affects the choice of antifungal therapy and treatment outcomes. Most C. auris isolates are resistant to fluconazole, and panresistant isolates have been described (13). All C. auris isolates in our study were resistant to fluconazole, and 40% were resistant to amphotericin B, both of which are commonly used in resource-limited countries; therefore, resistance to both classes of drug by C. auris is highly concerning because use of other antifungals such as echinocandins are limited in these countries.
Candidemia affected 2.5% of the COVID-19 patients in this cohort admitted to the ICU. In a tertiary care center in New Delhi, C. auris was reportedly the second most common Candida species that caused candidemia in non-COVID patients (14). Extensive contamination of the hospital environment has been detected in hospitals experiencing outbreaks of C. auris infection, warranting adherence to strict hospital infection prevention practices, such as enhanced cleaning of rooms with chlorine-based disinfectants at high concentrations (0.5%) for highly resistant pathogens such as C. auris. Critically ill COVID-19 patients with C. auris infection tend to have concurrent conditions (e.g., diabetes mellitus, chronic kidney disease) and risk factors (e.g., need for mechanical ventilation, receipt of steroids). To reduce complications, admission times in overburdened hospitals, and death rates among COVID-19 patients, identifying and treating C. auris infections is vital. A recent report that investigated changes in the fecal fungal microbiomes of COVID-19 patients has shown increasing prevalence of opportunistic fungal pathogens such as C. albicans, C. auris, and Aspergillus flavus (15). These data, along with our findings, provide evidence that the ongoing COVID-19 pandemic may provide ideal conditions for outbreaks of C. auris in hospital ICUs (4). Thus, during the COVID-19 pandemic, extra caution is warranted in hospitals, regions, cities, and countries where C. auris is prevalent.
A.C. and A. Sharma drafted the manuscript. A. Singh and B.T. collected the patient details and performed literature searches, identification, and susceptibility testing. All authors read and approved the manuscript.