Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 17;65(9):e0051721.
doi: 10.1128/AAC.00517-21. Epub 2021 Aug 17.

In Vitro Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa

Tsidiso G Maphanga  1 , Serisha D Naicker  1   2 , Stanford Kwenda  3 , Jose F Muñoz  4 , Erika van Schalkwyk  1 , Jeannette Wadula  5 , Trusha Nana  6 , Arshad Ismail  3 , Jennifer Coetzee  7 , Chetna Govind  8 , Phillip S Mtshali  3 , Ruth S Mpembe  1 , Nelesh P Govender  1   2   9 ; for GERMS-SA
Affiliations

In Vitro Antifungal Resistance of Candida auris Isolates from Bloodstream Infections, South Africa

Tsidiso G Maphanga et al. Antimicrob Agents Chemother. .

Abstract

Candida auris is a multidrug-resistant fungal pathogen that is endemic in South African hospitals. We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidemia in 2016 and 2017. We confirmed the species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using broth microdilution and Etest methods. We interpreted MICs using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared them to the C. auris B8441 reference strain. Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of ≥32 µg/ml), 19 (6%) to fluconazole and amphotericin B (MICs of ≥2 µg/ml), and 1 (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (resistant to fluconazole, amphotericin B, and echinocandins). Of 92 isolates selected for whole-genome sequencing, 77 clustered in clade III, including the pan-resistant isolates, 13 in clade I, and 2 in clade IV. Eighty-four of the isolates (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, and E343D in ERG11; N647T in MRR1; A651P, A657V, and S195G in TAC1b; S639P in FKS1HP1; and S58T in ERG3. Most South African C. auris isolates were resistant to azoles, although resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically susceptible isolates.

Keywords: Candida auris; antifungal resistance; candidemia; multidrug resistant; pan-drug resistant.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Distribution of known drug mutations within the ERG11 (Y132F, VF125AL, K117R, N335S, and E343D) (n = 5), MRR1 (N647T) (n = 1), TAC1b (S195G, A651P, and A657V) (n = 3), FKS1HP1 (S639P) (n = 1), and ERG3 (S58T) (n = 1) genes in 92 C. auris isolates. ERG11, MRR1, and TAC1b mutations are associated with fluconazole resistance, FKS1 mutations with echinocandin resistance, and ERG3 mutations with amphotericin B resistance.
See this image and copyright information in PMC

References

    1. Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA. 2018. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9:5346. 10.1038/s41467-018-07779-6. - DOI - PMC - PubMed
    1. Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, Tarai B, Singh A, Upadhyaya G, Upadhyay S, Yadav P, Singh PK, Khillan V, Sachdeva N, Perlin DS, Meis JF. 2018. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother 73:891–899. 10.1093/jac/dkx480. - DOI - PubMed
    1. Van Schalkwyk E, Mpembe RS, Thomas J, Shuping L, Ismail H, Lowman W, Karstaedt AS, Chibabhai V, Wadula J, Avenant T, Messina A, Govind CN, Moodley K, Dawood H, Ramjathan P, Govender NP. 2019. Epidemiologic shift in candidemia driven by Candida auris, South Africa, 2016–2017. Emerg Infect Dis 25:1698–1707. 10.3201/eid2509.190040. - DOI - PMC - PubMed
    1. Arendrup MC, Prakash A, Meletiadis J, Sharma C, Chowdhary A. 2017. Comparison of EUCAST and CLSI reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values. Antimicrob Agents Chemother 61:e00485-27. 10.1128/AAC.00485-17. - DOI - PMC - PubMed
    1. Centers for Disease Control and Prevention. 2020. Antifungal susceptibility testing and interpretation. https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html. Accessed 14 December 2020.

LinkOut - more resources