The dominance of triazole non-susceptible C. parapsilosis limits the choice of antifungal agents for management of candidaemia among critically ill neonates, children and adults in resource-limited South African hospitals.

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Introduction Candida auris is a multidrug-resistant fungal pathogen endemic in South African hospitals. Materials and methods We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidaemia, 2016-2017. We confirmed species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole and flucytosine using broth microdilution (BMD) and Etest. We interpreted minimum inhibitory concentrations (MICs) using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared to the C. auris B8441 reference strain. Results Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (85%) to fluconazole alone (MIC of ≥32 mg/L), 19 (5%) to fluconazole and amphotericin B (MIC ≥2 mg/L) and one (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (fluconazole, amphotericin B, echinocandins). Of 93 isolates selected for whole genome sequencing, 78 clustered in clade III including the pan-resistant isolates, 13 in clade I and two in clade IV. Eighty-four of these (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, E343D in ERG11 ; N647T in MRR1; A651P, A657V, S195G in TAC1b; S639P in FKS1; and S58T in ERG3 genes. Conclusions Most South African C. auris isolates were resistant to azoles, though resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically-susceptible isolates.