CANDIDA HAEMULONII AND CANDIDA AURIS: EMERGING MULTIDRUG RESISTANT CANDIDA SPECIES

Background

Candida haemulonii and Candida auris are recently described, closely related multidrug resistant Candida species. Little is known about the pathogenicity and epidemiological characteristics of these species.

Methods

We reviewed Candida clinical isolates recovered from 1/2008 through 6/2015 at the Tel Aviv Medical Center. Species identification was done using ITS1-ITS2 PCR and sequencing. We determined susceptibility to antifungals and efflux transporter activity. Virulence was assessed by intravenous infection of BALB/c mice immunosuppressed with cyclophosphamide.

Results

Thirty-nine patient-unique isolates were identified as C. haemulonii by Vitek 2, of which 21 (54%) were from patients receiving care at a peripheral vascular disease outpatient clinic. Predisposing factors were diabetes mellitus type 2, end-stage renal disease, and the use of topical azoles. Isolates were recovered from wounds (21), urine (11), blood (5), and vascular catheter (2). Of 9 isolates available for microbiological analysis, all 5 blood isolates were identified by ITS sequencing as C. auris, whereas 4 non-invasive isolates were identified as C. haemulonii. C. auris, but not C. haemulonii, was thermotolerant to 40⁰C. C. auris was highly lethal in immunosuppressed mice, whereas C. haemulonii was avirulent in this model (log rank test for survival, P<0.001). C. auris isolates were closely related to each other and phylogenetically distinct from isolates recovered in East Asia and South Africa. All isolates exhibited high MIC for fluconazole (MIC50, [range]), 32 mcg/mL (16-64 mcg/mL), anidulafungin, 8 mcg/mL (4-8 mcg/mL), and amphotericin B, 2 mcg/mL (1-2 mcg/mL). Transmembrane efflux activity was ~3 times that observed with C. glabrata.

Conclusions

These are the first reported cases of clinical infection with C. auris and C. haemulonii in Israel. The emergence of multidrug resistant Candida warrants enhanced vigilance.