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Multilaboratory Study of Epidemiological Cutoff Values for Detection of Resistance in Eight Candida Species to Fluconazole, Posaconazole, and Voriconazole
Open accessAbstract
Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n=11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 μg/ml for C. albicans, 0.5, 0.25, and 0.03 μg/ml for C. dubliniensis, 8, 1, and 0.25 μg/ml for C. glabrata, 8, 0.5, and 0.12 μg/ml for C. guilliermondii, 32, 0.5, and 0.25 μg/ml for C. krusei, 1, 0.06, and 0.06 μg/ml for C. lusitaniae, 1, 0.25, and 0.03 μg/ml for C. parapsilosis, and 1, 0.12, and 0.06 μg/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.
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“With respect to CLSI clinical breakpoints, fluconazole resistance, defined as MIC values ≥8 mg/L for C. albicans, has been reported overall to be as high as 3.5%.43–48”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [48]
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Clinical and Laboratory Standards Institute
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- Clinical and Laboratory Standards Institute. 2008. M27-A3. Reference method for broth dilution antifungal susceptibility testing of yeasts, 3rd ed. Clinical and Laboratory Standards Institute, Wayne, PA.
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Barroso, V. D. M. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2023.tde-15092023-110730
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Self-citationLockhart, S. R., & Berkow, E. L. (2023) · ClinMicroNow · doi:10.1002/9781683670438.mcm0133
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Challenges in establishing epidemiological cut-off values for the Burkholderia cepacia complex
Huse, H., Manuel, C., McLemore, T., Humphries, R. M., Galdino, A. C. M., Celedonio, D., LiPuma, J. J., Green, D. A., Zlosnik, J. E. A., Traczewski, M. M., et al. (2026) · Journal of Clinical Microbiology · doi:10.1128/jcm.00730-26
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Metadata
- Authors
- Espinel-Ingroff, A., Pfaller, M. A., Bustamante, B., Canton, E., Fothergill, A., Fuller, J., Gonzalez, G. M., Lass-Flörl, C., Lockhart, S. R., Martin-Mazuelos, E., Meis, J. F., Melhem, M. S. C., Ostrosky-Zeichner, L., Pelaez, T., Szeszs, M. W., St-Germain, G., Bonfietti, L. X., Guarro, J., & Turnidge, J.
- Affiliations
- VCU Medical Center, Richmond, Virginia, USA
- University of Iowa (US)
- Universidad Peruana Cayetano Heredia (PE)
- Unidad de Microbiologia Experimental, Centro de Investigacion, Hospital Universitario La Fe, Valencia, Spain
- The University of Texas at San Antonio Health Science Center (US)
- University of Alberta (CA)
- Universidad Autonóma de Nuevo León, Monterrey, Nuevo León, Mexico
- The Innsbruck Medical University, Division of Hygiene and Medical Microbiology, Innsbruck, Austria
- Centers for Disease Control and Prevention (US)
- Hospital Universitario de Valme, Seville, Spain
- Radboud University Nijmegen (NL)
- Fungal Taxonomy Laboratories, Adolfo Lutz Institute, São Paulo City, Brazil
- University of Texas Health Science Center, Houston, Texas, USA
- Hospital General Universitario Gregorio Maraňón, Facultad de Medicina, Universidad Complutense, Madrid, Spain
- Instituto Adolfo Lutz (BR)
- Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Quebec, Canada
- Institut de Recerca Biomèdica Catalunya Sud (ES)
- The University of Adelaide (AU)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2014-04
- Volume
- 58
- Issue
- 4
- Pages
- 2006-2012
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC4023759
- OpenAlex
- W2113614834
- Cited by
- 105
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 11 · 2015: 18 · 2014: 6
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Rovira & Virgili repository (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Microbiology › Yeasts and Rust Fungi Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Keywords
- epidemiological cut-off values, Candida, antifungal resistance, fluconazole, posaconazole, voriconazole, triazole antifungals, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida lusitaniae, Candida guilliermondii, Candida dubliniensis
- MeSH terms
- Antifungal Agents, Candida, Microbial Sensitivity Tests, Pyrimidines, Triazoles, Fluconazole, Voriconazole
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