Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: Time for harmonization of CLSI and EUCAST broth microdilution methods
Abstract
Background Both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have MIC clinical breakpoints (CBPs) for fluconazole (FLU) and Candida. EUCAST CBPs are species-specific, and apply only to C. albicans, C. tropicalis and C. parapsilosis, while CLSI CBPs apply to all species. We reassessed the CLSI CBPs for FLU and Candida in light of recent data.Methods We examined (1) molecular mechanisms of resistance and cross-resistance profiles, (2) wild-type (WT) MICs and epidemiological cutoff values (ECVs) for FLU and major Candida species by both CLSI and EUCAST methods, (3) determination of essential (EA) and categorical agreement (CA) between CLSI and EUCAST methods, (4) correlation of MICs with outcomes from previously published data using CLSI and EUCAST methods, and (5) pharmacokinetic and pharmacodynamic considerations. We applied these findings to propose new species-specific CLSI CBPs for FLU and Candida.Results WT distributions from large collections of Candida revealed similar ECVs by both CLSI and EUCAST methods (0.5-1 mcg/ml for C. albicans, 2 mcg/ml for C. parapsilosis and C. tropicalis, 32 mcg/ml for C. glabrata, and 64-128 for C. krusei). Comparison of CLSI and EUCAST MICs reveal EA and CA of 95% and 96%, respectively. Datasets correlating CLSI and EUCAST FLU MICs with outcomes revealed decreased response rates when MICs were > 4 mcg/ml for C. albicans, C. tropicalis and C. parapsilosis, and > 16 mcg/ml for C. glabrata.Conclusions Adjusted CLSI CBPs for FLU and C. albicans, C. parapsilosis, C. tropicalis (S, ≤ 2 mcg/ml; SDD, 4 mcg/ml; R, ≥ 8 mcg/ml), and C. glabrata (SDD, ≤ 32 mcg/ml; R, ≥ 64 mcg/ml) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs.
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In 2012, fluconazole breakpoints were revised to account for species-specific differences in drug response, as well as to enhance sensitivity to detect the emergence of fluconazole-resistant strains.
“In 2012, these breakpoints were revised to account for species-specific differences in drug response, as well as to enhance sensitivity to detect the emergence of fluconazole-resistant strains [47].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [47]
Susceptibility testing to fluconazole using CLSI or EUCAST broth microdilution methodology produces MIC values that correlate reasonably well with the likelihood of successful treatment outcomes.
“Susceptibility testing to fluconazole using CLSI or EUCAST broth microdilution methodology produces MIC values that correlate reasonably well with the likelihood of successful treatment outcomes [46,47].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [47]
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References 114 · Cited by 314
- Authors
- Pfaller, M. A., Andes, D., Diekema, D. J., Espinel-Ingroff, A., & Sheehan, D.
- Affiliations
- University of Iowa (US)
- University of Wisconsin–Madison (US)
- Pfizer (United States) (US)
- Venue
- Drug Resistance Updates
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 13
- Issue
- 6
- Pages
- 180-195
- ISSN
- 1368-7646 (ISSN-L)
- OpenAlex
- W1998771714
- Cited by
- 314
- References
- 114
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 6 · 2020: 9 · 2019: 13 · 2018: 18 · 2017: 18 · 2016: 19 · 2015: 27 · 2014: 33 · 2013: 36 · 2012: 53
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Resistance Updates (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- fluconazole, Candida, clinical breakpoints, epidemiological cut-off values, CLSI, EUCAST, broth microdilution, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei, antifungal resistance, cross-resistance, measurement agreement, pharmacokinetics, pharmacodynamics
- MeSH terms
- Candida, Candidiasis, Europe, Humans, Microbial Sensitivity Tests, Species Specificity, United States, Fluconazole, Drug Resistance, Fungal
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