Multilocus sequence typing of azole-resistant Candida auris strains, South Africa

Abstract

Background: Candida auris is an emerging multidrug-resistant fungal pathogen associated with high mortality.Methods: We investigated the genetic relatedness of clinical C. auris isolates from patients admitted to either public- or private-sector hospitals, which were submitted to a reference laboratory from 2012 to 2015. Patient demographics and clinical details were recorded. We performed antifungal susceptibility testing, sequencing of the hotspot 1 and 2 regions of the FKS1 and FKS2 genes for all isolates with an echinocandin minimum inhibitory concentration (MIC) of ≥1 µg/mL and cluster analysis using multilocus sequence typing.Results: Eighty-five isolates were confirmed as C. auris. The median patient age was 59 years [inter-quartile range (IQR): 48–68 years], with male patients accounting for 68% of cases. Specimen types included urine (29%), blood (27%), central venous catheter tips (25%), irrigation fluid (7%), tissue (5%), respiratory tract specimens (4%) and other (3%). Ninety-seven per cent of isolates were resistant to fluconazole, 7% were resistant to both fluconazole and voriconazole, 8% were resistant to both fluconazole and echinocandins (considered multidrug resistant) and all were susceptible to amphotericin B. Of the 15 randomly selected fluconazole-resistant isolates, 14 isolates had an isavuconazole MIC ≤ 1 µg/mL. No FKS mutations were detected. Multilocus sequence typing (MLST) analysis grouped isolates into two clusters: cluster 1 and cluster 2 comprising 83 and 2 isolates, respectively.Conclusions: Azole-resistant C. auris strains circulating in South African hospitals were related by MLST, but the possibility of nosocomial transmission should be explored using a more discriminatory technique, for example, whole genome sequencing.

Candida auris: a Review of the Literature

“…Treatment failure with fluconazole has been reported for fluconazole-sensitive isolates in the United States (9). Reduced susceptibility to other triazole antifungals, including voriconazole, itraconazole, and isavuconazole, has also been demonstrated (26,41,52,53). In addition, there is variability in the susceptibilities of isolates to amphotericin B (4,6,8,9,17,20,22,23,30,52,54,55).…”

Emergence of Clonally-Related South Asian Clade I Clinical Isolates of Candida auris in a Greek COVID-19 Intensive Care Unit

“…Epidemiological investigations may elucidate the modes of C. auris nosocomial transmission. Previous studies by using MLST have shown that that C. auris strains are highly related despite being isolated from patients admitted to a large number of hospitals, suggesting that clonal strains are circulating or that the method is insufficiently discriminatory [ 38 ]. On the other hand, a microsatellite system for a largely clonal pathogen is a labor-intensive process.…”

Candida auris: an emergent virulent and multidrug-resistant yeast associated with serious health implications

“…The resistance of C. auris to echinocandins is associated with natural variations or mutations within conserved hot-spot regions of the FKS-encoded protein, leading to amino acid variations in two conserved hot-spot regions of either FKS1 or, more frequently, in the paralog FKS2 in C. glabrata [65]. Interestingly, Magobo [66] reported that no mutation was documented from the FKS1/2 hotspots, even among the C. auris strains with relatively high echinocandin MICs. Magobo et al [66] attributed phenotypic echinocandin resistance of the isolates to mechanisms such as enhanced chitin expression and other point mutations outside the hotspot regions of FKS1/2 genes.…”