Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

Abstract

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Keywords: COVID-19; Candida auris; Israel; SARS-CoV-2; antifungal susceptibility; coronavirus disease; drug resistance; epidemiology; fungi; multilocus sequence typing; respiratory infections; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figure 1

Incidence (no. cases) of Candida auris infection by medical facility (A) and type of specimen (B), Israel, 2014–2022. Epidemic plots were constructed with each patient appearing once, on the date of the first C. auris–positive specimen. H, hospital; NH, nursing home.

Figure 2

Association of Candida auris infection with COVID-19 hospitalization, Israel, January 2021–May 2022. Bars represent monthly C. auris incidence (no. cases). Cases with SARS-CoV-2 co-infection are shown in orange, non–co-infected cases are in blue. Red line shows level of hospital occupancy with COVID-19 patients. Scales for the y-axes differ substantially to underscore patterns but do not permit direct comparisons.

Figure 3

Minimum spanning trees of Candida auris strains for 2014–2020 (A) and 2014–2022 (B), Israel. Genetic relatedness of C. auris isolates was assessed using multilocus sequence typing. Strain cluster designation was determined using sequences published by Kwon et al. (shown in gray nodes) (17). Nodes are colored according to the respective medical center. Nodes marked with asterisks represent 2016 importation event from South Africa. C, clade; H, hospital; NH, nursing home.

Figure 4

Association of population strain clustering with antifungal drug MIC and medical facility for Candida auris strains, Israel. A phylogenetic tree of C. auris isolates was constructed using multilocus sequence typing and Bayesian inference. Text colors represent different medical centers. Heat map colors represent MIC of each drug, ranging from fully susceptible (yellow) to resistant (dark blue). AMB, amphotericin B; ANF, anidulafungin; FCZ, fluconazole; VCZ, voriconazole.

Figure 5

Comparison of antifungal MIC distribution among Candida auris clades, Israel. Antifungal MICs were determined using Clinical Laboratory Standards Institute M27A3/S4 methodology, for fluconazole (A), voriconazole (B), amphotericin B (C), and anidulafungin (D). Comparison among C. auris clades was done using the Kruskal-Wallis test and the pairwise Wilcoxon post-hoc test. Each dot represents a patient-specific isolate. Horizontal bars within box plots indicate medians, box tops and bottoms represent 95% confidence interval. NS, not significant.

Figure 6

Temporal distribution of Candida auris clades and their respective MIC values, Israel. Distribution of C. auris fluconazole and voriconazole MIC is shown for January 2014–May 2022. Each dot represents a patient-specific isolate. High fluconazole and voriconazole MIC associated with clade III is noted in 2021 and 2022.

Figure 7

Hospital-level outbreak time course for the 3 hospitals with the largest Candida auris case numbers, Israel. Time course of C. auris hospital outbreaks is shown for patients receiving mechanical ventilation (A) and patients not receiving mechanical ventilation (B). Individual patients are displayed in bottom to top order according to the first date they became infected. Bars are plotted from the date of first C. auris–positive specimen to the date of hospital discharge. Colors represent hospital unit at the time C. auris was recovered. COVID-19, specialized COVID-19 unit; H, hospital; ICU, intensive care unit; INT-A, intermediate care unit A; INT-B, intermediate care unit B.