Rate of FKS Mutations among Consecutive Candida Isolates Causing Bloodstream Infection
Open accessAbstract
Precise FKS mutation rates among Candida species are undefined because studies have not systematically screened consecutive, disease-causing isolates. The Sensititre YeastOne (SYO) assay measures echinocandin MICs against Candida with less variability than reference broth microdilution methods. However, clinical breakpoint MICs may overstate caspofungin nonsusceptibility compared to other agents. Our objectives were to determine CandidaFKS mutation rates by studying consecutive bloodstream isolates and to determine if discrepant susceptibility results were associated with FKS mutations.FKS hot spots were sequenced in echinocandin-intermediate and -resistant isolates and those from patients with breakthrough candidemia or ≥3 days of prior echinocandin exposure. Overall, 453 isolates from 384 patients underwent susceptibility testing; 16% were echinocandin intermediate or resistant. Intermediate susceptibility rates were higher for Candida glabrata than for other species (P< 0.0001) and higher for caspofungin than for other agents (P< 0.0001). Resistance rates were similar between agents.FKS mutations were detected in 5% of sequenced isolates and 2% of isolates overall. Corresponding rates among C. glabrata isolates were 8% and 4%, respectively. Among Candida albicans isolates, rates were 5% and <1%, respectively. Mutations occurred exclusively with prior echinocandin exposure and were not detected in other species. Isolates with discrepant susceptibility results did not harbor FKS mutations. Mutation rates among isolates resistant to ≥2, 1, and 0 agents were 75%, 13%, and 0%, respectively. In conclusion,FKS mutations were uncommon among non-C. glabrata species, even with prior echinocandin exposure. Discrepancies in echinocandin susceptibility by SYO testing were not driven by mutations and likely reflect imprecise caspofungin clinical breakpoints.
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A review of the most recent data suggests that many, but not all, breakthrough Candida infections occur due to organisms that are resistant to one or more antifungals, and are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.
“A review of the most recent data pertaining to BT Candida infections suggests that many, but not all, of these infections occur due to organisms that are resistant to one or more antifungals, and accordingly are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.89–92”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [90]
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Hikida, S., Akiyama, Y., Ishikane, M., Shimazu, H., Nasu, R., Shinohara, T., Nagi, M., Shirai, R., Onakado, M., Nakayama, N., et al. (2025) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2025.102856 · Cited by 1 · see citing works
Genetic determinants of antifungal resistance in Candida species
Silva, D. B. D. S., Barufatti, A., & Kelly, M. P. D. O. (2016) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb2016.15295
Lepak, A. J., & Andes, D. R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819990-9.00018-4
Ciências Biológicas e da Saúde: integrando saberes em diferentes contextos - Volume 3
Barbosa Neto, O., Praxedes, M. F. D. S., Silva, P. F. D., & Carvalho Junior, F. F. D. (2023) · Editora Científica Digital eBooks · doi:10.37885/978-65-5360-335-6
- Authors
- Shields, R. K., Nguyen, M. H., Press, E. G., Cumbie, R., Driscoll, E., Pasculle, A. W., & Clancy, C. J.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2015-12
- Volume
- 59
- Issue
- 12
- Pages
- 7465-7470
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC4649226
- OpenAlex
- W2179911245
- Cited by
- 55
- References
- 30
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 1
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-02-26)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (KL2TR000146)
- National Institute of Allergy and Infectious Diseases (K08AI114883)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida, bloodstream infection, echinocandin resistance, caspofungin, Candida glabrata, Candida albicans, Sensititre YeastOne
- MeSH terms
- Caspofungin, Micafungin, Antifungal Agents, Candida, Candidiasis, Fungal Proteins, Humans, Microbial Sensitivity Tests, Drug Resistance, Fungal, Candida glabrata, Echinocandins, Lipopeptides, Mutation Rate
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