Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

Pfaller, M. A.; Diekema, D. J.; Ostrosky-Zeichner, L.; Rex, J. H.; Alexander, B. D.; Andes, D.; Brown, S. D.; Chaturvedi, V.; Ghannoum, M. A.; Knapp, C. C.; Sheehan, D. J.; Walsh, T. J.

doi:10.1128/jcm.00566-08

Cited by 250Antifungal resistance and susceptibilityFungal Plant Pathogen ControlYeasts and Rust Fungi Studies

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

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Pfaller, M. A., Diekema, D. J., Ostrosky-Zeichner, L., Rex, J. H., Alexander, B. D., Andes, D., Brown, S. D., Chaturvedi, V. +4 more·2008·Journal of Clinical Microbiology

DOI 10.1128/jcm.00566-08PMC PMC2519503

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Abstract

The CLSI Antifungal Subcommittee followed the M23-A2 “blueprint” to develop interpretive MIC breakpoints for anidulafungin, caspofungin, and micafungin against Candida species. MICs of ≤2 μg/ml for all three echinocandins encompass 98.8 to 100% of all clinical isolates of Candida spp. without bisecting any species group and represent a concentration that is easily maintained throughout the dosing period. Data from phase III clinical trials demonstrate that the standard dosing regimens for each of these agents may be used to treat infections due to Candida spp. for which MICs are as high as 2 μg/ml. An MIC predictive of resistance to these agents cannot be defined based on the data from clinical trials due to the paucity of isolates for which MICs exceed 2 μg/ml. The clinical data set included only three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were >2 μg/ml (two C. parapsilosis isolates at 4 μg/ml and one C. rugosa isolate at 8 μg/ml). Based on these data, the CLSI subcommittee has decided to recommend a “susceptible only” breakpoint MIC of ≤2 μg/ml due to the lack of echinocandin resistance in the population of Candida isolates thus far. Isolates for which MICs exceed 2 μg/ml should be designated “nonsusceptible” (NS). For strains yielding results suggestive of an NS category, the organism identification and antimicrobial-susceptibility test results should be confirmed. Subsequently, the isolates should be submitted to a reference laboratory that will confirm the results by using a CLSI reference dilution method.

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Clinical trial data with all 3 echinocandins have shown that the available drugs can be used successfully to treat C. parapsilosis infections with increased MICs.
“Clinical trial data with all 3 echinocandins have shown that the available drugs can be used successfully to treat C parapsilosis infections with increased MICs.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [167]

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Authors: Pfaller, M. A., Diekema, D. J., Ostrosky-Zeichner, L., Rex, J. H., Alexander, B. D., Andes, D., Brown, S. D., Chaturvedi, V., Ghannoum, M. A., Knapp, C. C., Sheehan, D. J., & Walsh, T. J.
Affiliations: University of Iowa (US)
University of Texas, Houston, Texas
AstraZeneca (United Kingdom) (GB)
Duke University (US)
University of Wisconsin–Madison (US)
The Clinical Microbiology Institute, Wilsonville, Oregon
New York State Department of Health (US)
Case Western Reserve University (US)
Trek Diagnostic Systems, Cleveland, Ohio
Pfizer (United States) (US)
National Institutes of Health (US)
Corresponding author: Pfaller, M. A.
ORCID: Pfaller, M. A.
Diekema, D. J.
Rex, J. H.
Alexander, B. D.
Andes, D.
Brown, S. D.
Chaturvedi, V.
Ghannoum, M. A.
Walsh, T. J.
Venue: Journal of Clinical Microbiology
Publisher: American Society for Microbiology
Published: 2008-08
Volume: 46
Issue: 8
Pages: 2620-2629
ISSN: 0095-1137 (ISSN-L)
1098-660X
DOI: 10.1128/jcm.00566-08
PMC: PMC2519503
OpenAlex: W2100967944
Cited by: 250
References: 61
Citations by year: 2026: 5 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 15 · 2014: 11 · 2013: 14 · 2012: 17
FWCI: 29.73
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Clinical Microbiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Food and Drug Administration
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 › Yeasts and Rust Fungi Studies
Keywords: Candida, echinocandins, caspofungin, anidulafungin, micafungin, antifungal susceptibility, Candida parapsilosis, Candida rugosa, antifungal resistance
MeSH terms: Caspofungin, Micafungin, Anidulafungin, Antifungal Agents, Candida, Candidiasis, Clinical Trials as Topic, Humans, Lipoproteins, Microbial Sensitivity Tests, Statistics as Topic, Treatment Outcome, Drug Resistance, Fungal, Echinocandins, Lipopeptides

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Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

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