Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: Should the clinical laboratory be testing this agent?
Open accessAbstract
Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
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EUCAST or CLSI methods are not recommended for testing susceptibility towards caspofungin due to a lack of reproducibility across laboratories or drug batches and paradoxical growth of Candida at concentrations above MIC.
“For example, these methods are not recommended for testing the susceptibility towards caspofungin (an echinocandin), given a lack of reproducibility across laboratories or even drug batches [120] and the paradoxical growth of Candida at concentrations above MIC [121].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [120]
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References 23 · Cited by 216
- Authors
- Espinel-Ingroff, A., Arendrup, M. C., Pfaller, M. A., Bonfietti, L. X., Bustamante, B., Canton, E., Chryssanthou, E., Cuenca-Estrella, M., Dannaoui, E., Fothergill, A., Fuller, J., Gaustad, P., Gonzalez, G. M., Guarro, J., Lass-Flörl, C., Lockhart, S. R., Meis, J. F., Moore, C. B., Ostrosky-Zeichner, L., Pelaez, T., Pukinskas, S. R. B. S., St-Germain, G., Szeszs, M. W., & Turnidge, J.
- Affiliations
- Virginia Commonwealth University Medical Center, Richmond, Virginia, USA
- Statens Serum Institut (DK)
- University of Iowa (US)
- Instituto Adolfo Lutz (BR)
- Universidad Peruana Cayetano Heredia (PE)
- Unidad de Microbiologia Experimental, Centro de Investigacion, Hospital Universitario La Fe, Valencia, Spain
- Karolinska University Hospital (SE)
- Department of Mycology, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
- Institut Pasteur, Centre National de Reference Mycoses and Antifongiques, Unite de Mycologie Moleculaire, Paris, France
- The University of Texas at San Antonio Health Science Center (US)
- University of Alberta (CA)
- Oslo University Hospital (NO)
- Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
- Institut de Recerca Biomèdica Catalunya Sud (ES)
- The Innsbruck Medical University, Division of Hygiene and Medical Microbiology, Innsbruck, Austria
- Centers for Disease Control and Prevention (US)
- Radboud University Nijmegen (NL)
- Mycology Reference Centre, Education and Research Centre, University Hospital of South Manchester, Manchester, United Kingdom
- University of Texas Health Science Center, Houston, Texas, USA
- Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain
- Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Québec, Canada
- The University of Adelaide (AU)
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2013-12
- Volume
- 57
- Issue
- 12
- Pages
- 5836-5842
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3837874
- OpenAlex
- W2164149772
- Cited by
- 216
- References
- 23
- Citations by year
- 2026: 13 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 17 · 2020: 21 · 2019: 21 · 2018: 17 · 2017: 21 · 2016: 26 · 2015: 23 · 2014: 25 · 2013: 6
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Universidad Peruana Cayetano Heredia Institutional Repository (submittedVersion, cc-by-nc-nd)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Centers for Disease Control and Prevention
- 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
- caspofungin, Candida, inter-laboratory variability, echinocandin susceptibility, clinical breakpoints, MIC distribution, Candida glabrata, Candida krusei, Candida albicans, Candida tropicalis, Candida dubliniensis, Candida lusitaniae, Candida parapsilosis, Candida guilliermondii, antifungal susceptibility testing, micafungin, anidulafungin
- MeSH terms
- Caspofungin, Micafungin, Anidulafungin, Antifungal Agents, Candida, Candidiasis, Europe, Humans, Microbial Sensitivity Tests, North America, South America, Species Specificity, Observer Variation, Drug Resistance, Fungal, Echinocandins, Lipopeptides
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