Breakpoints for antifungal agents: An update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp.
Abstract
Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations. Therefore, accurate susceptibility testing and appropriate clinical breakpoints for the interpretation of susceptibility results have become increasingly important. Here we review the underlying methodology by which breakpoints have been selected by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Five parameters are evaluated: dosing regimens used; EUCAST MIC distributions from multiple laboratories, species and compound specific epidemiological cut off values (upper MIC limits of wild type isolates or ECOFFs), pharmacokinetic/pharmacodynamic relationships and targets associated with outcome and finally clinical data by species and MIC when available. The general principles are reviewed followed by a detailed review of the individual aspects for Candida species and the three echinocandins and for Aspergillus and the three mould-active azoles. This review provides an update of the subcommittee on antifungal susceptibility testing (AFST) of the EUCAST methodology and summarises the current EUCAST breakpoints for Candida and Aspergillus. Recommendations about applicability of antifungal susceptibility testing in the routine setting are also included.
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Novel FKS Mutations Associated with Echinocandin Resistance in Candida Species
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Azole Resistance in Aspergillus : A Growing Public Health Menace
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Azole‐Resistant Central Nervous System Aspergillosis
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Perkhofer, S., Lechner, V., & Lass‐Flörl, C. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01530-08 · Cited by 80 · see citing works
Self-citationCampoli, P., Abdallah, Q. A., Robitaille, R., Solis, N. V., Fielhaber, J. A., Kristof, A. S., Laverdière, M., Filler, S. G., & Sheppard, D. C. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00637-11 · Cited by 77 · see citing works
Pfaller, M. A., Chaturvedi, V. P., Diekema, D. J., Ghannoum, M. A., Holliday, N. M., Killian, S. B., Knapp, C. C., Messer, S. A., Miskou, A., & Ramani, R. (2012) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2012.05.008 · Cited by 75 · see citing works
Jensen, R. H., & Arendrup, M. C. (2011) · Journal of Clinical Microbiology · doi:10.1128/jcm.02071-10 · Cited by 68 · see citing works
Self-citationAzole-Resistant Invasive Aspergillosis: Relationship to Agriculture
Stensvold, C. R., Jørgensen, L. N., & Arendrup, M. C. (2012) · Current Fungal Infection Reports · doi:10.1007/s12281-012-0097-7 · Cited by 67 · see citing works
Self-citationArendrup, M. C., Pfaller, M. A., & the Danish Fungaemia Study Group (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00355-12 · Cited by 67 · see citing works
Self-citationCuenca‐Estrella, M., Gómez‐López, A., Mellado, E., & Rodriguez-Tudela, J. L. (2005) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2005.01166.x · Cited by 66 · see citing works
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Self-citationArendrup, M. C., Kahlmeter, G., Rodrı́guez-Tudela, J. L., & Donnelly, J. P. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01624-08 · Cited by 62 · see citing works
Self-citationEUCAST Technical Note on voriconazole
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Self-citationRapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin
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Shields, R. K., Nguyen, M. H., Press, E. G., Updike, C. L., & Clancy, C. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01451-13 · Cited by 56 · see citing works
Slater, J. L., Howard, S. J., Sharp, J., Goodwin, J., Gregson, L., Alastruey‐Izquierdo, A., Arendrup, M. C., Warn, P. A., Perlin, D. S., & Hope, W. W. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01686-10 · Cited by 52 · see citing works
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EUCAST technical note on Amphotericin B
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Self-citationJensen, R. H., Johansen, H. K., & Arendrup, M. C. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01193-12 · Cited by 47 · see citing works
Self-citation<scp>EUCAST</scp> Technical Note on <i>Candida</i> and micafungin, anidulafungin and fluconazole
Cavling Arendrup, M., Cuenca‐Estrella, M., Lass‐Flörl, C., Hope, W. W., & The European Committee on Antimicrobial Susceptibility Testing – Subcommittee on Antifungal Susceptibility Testing (EUCAST‐AFST) (2014) · Mycoses · doi:10.1111/myc.12170 · Cited by 43 · see citing works
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Self-citationEUCAST breakpoints for antifungals
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Self-citationCandida spp. with Acquired Echinocandin Resistance, France,
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Self-citation
- Authors
- Arendrup, M. C., Cuenca-Estrella, M., Lass-Flörl, C., & Hope, W. W.
- Affiliations
- Statens Serum Institut (DK)
- University of Liverpool (GB)
- Corresponding author
- Arendrup, Maiken C.
- Venue
- Drug Resistance Updates
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 16
- Issue
- 6
- Pages
- 81-95
- ISSN
- 1368-7646 (ISSN-L)
- OpenAlex
- W2017430996
- Cited by
- 129
- References
- 133
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 11 · 2017: 15 · 2016: 19 · 2015: 21 · 2014: 10 · 2012: 1
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Resistance Updates (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute for Health and Care Research
- 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 › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- antifungal susceptibility breakpoints, EUCAST, echinocandins, triazoles, Candida, Aspergillus, epidemiological cut-off values, antifungal resistance, susceptibility testing, pharmacokinetic-pharmacodynamic relationship, dosing regimen
- MeSH terms
- Animals, Antifungal Agents, Aspergillosis, Aspergillus, Candida, Candidiasis, Humans, Microbial Sensitivity Tests, Triazoles, Drug Resistance, Fungal, Echinocandins
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