Cited by 55Antifungal resistance and susceptibilityYeasts and Rust Fungi StudiesFungal and yeast genetics research

Molecular characterisation of Candida auris isolates from immunocompromised patients in a tertiary‐care hospital in Kuwait reveals a novel mutation in FKS1 conferring reduced susceptibility to echinocandins

Asadzadeh, Mohammad, Mokaddas, Eiman, Ahmad, Suhail, Abdullah, Aneesa A., de Groot, Theun, Meis, Jacques F., Shetty, Shama A.·2022·Mycoses

Abstract

Summary: Background: Candida auris is an emerging, potentially multidrug‐resistant pathogen that exhibits clade‐specific resistance to fluconazole and also develops resistance to echinocandins and amphotericin B easily. This study analysed 49 C auris isolates for alterations in hotspot‐1 and hotspot‐2 of FKS1 for the detection of mutations conferring reduced susceptibility to echinocandins. Methods: C auris isolates (n = 49) obtained from 18 immunocompromised patients during June 2016‐December 2018 were analysed. Antifungal susceptibility testing was performed by Etest and broth microdilution‐based MICRONAUT‐AM assay. Mutations in hotspot‐1 and hotspot‐2 regions of FKS1 were detected by PCR sequencing and fingerprinting of the isolates was done by short tandem repeat typing. Results: The patients had multiple comorbidities/risk factors for Candida spp. infection including cancer/leukaemia/lymphoma/myeloma (n = 16), arterial/central line (n = 17), urinary catheter (n = 17), mechanical ventilation (n = 14) and major surgery (n = 9) and received antifungal drugs as prophylaxis and/or empiric treatment. Seven patients developed C auris candidemia/breakthrough candidemia, nine patients had candiduria with/without candidemia and four patients developed surgical site/respiratory infection. Resistance to fluconazole and amphotericin B was detected in 44 and four isolates, respectively. Twelve C auris isolates from eight patients showed reduced susceptibility to echinocandins. Seven isolates contained hostspot‐1 mutations and three isolates from a candidemia patient contained R1354H mutation in hotspot‐2 of FKS1. Ten patients died, five were cured, two were lost to follow‐up and treatment details for one patient were not available. Conclusions: Our findings describe development of a novel mutation in FKS1 conferring reduced susceptibility to echinocandins in one patient during treatment and unfavourable clinical outcome for many C auris‐infected patients.

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Crossref · 10.1111/myc.13419

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  • Several amino acid substitutions in FKS1 have been associated with decreased echinocandin susceptibility in C. auris.

    “Several amino acid substitutions in FKS1 have also been associated with decreased echinocandin susceptibility in C. auris12,37–42.”

    From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [40]

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Authors
Asadzadeh, M., Mokaddas, E., Ahmad, S., Abdullah, A. A., de Groot, T., Meis, J. F., & Shetty, S. A.
Affiliations
  • Kuwait University (KW)
  • Ibn Sina Hospital (KW)
  • Department of Medical Microbiology and Infectious Diseases Canisius Wilhelmina Hospital Nijmegen The Netherlands
  • Radboud University Medical Center (NL)
Corresponding author
Ahmad, Suhail
Venue
Mycoses
Publisher
Wiley
Published
2022-01-03
Volume
65
Issue
3
Pages
331-343
ISSN
  • 0027-5557 (ISSN-L)
  • 0933-7407
  • 1439-0507
OpenAlex
W4200483743
Cited by
55
References
83
Citations by year
2026: 7 · 2025: 13 · 2024: 12 · 2023: 17 · 2022: 6
FWCI
2.77
Type
journal article
Language
en
Open access
closed
Locations
  • Mycoses (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida auris, echinocandin resistance, FKS1 mutations, immunocompromised patients, candidemia, candiduria, antifungal resistance, fluconazole resistance, amphotericin B resistance, short tandem repeat typing, molecular characterization
MeSH terms
Candida auris, Antifungal Agents, Humans, Kuwait, Microbial Sensitivity Tests, Mutation, Immunocompromised Host, Drug Resistance, Fungal, Echinocandins, Candidemia, Tertiary Care Centers

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