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Mycology

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

M. A. Pfaller, D. J. Diekema, L. Ostrosky-Zeichner, J. H. Rex, B. D. Alexander, D. Andes, S. D. Brown, V. Chaturvedi, M. A. Ghannoum, C. C. Knapp, D. J. Sheehan, T. J. Walsh
M. A. Pfaller
1University of Iowa, Iowa City, Iowa
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  • For correspondence: michael-pfaller@uiowa.edu
D. J. Diekema
1University of Iowa, Iowa City, Iowa
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L. Ostrosky-Zeichner
2University of Texas, Houston, Texas
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J. H. Rex
3AstraZenica, Macclesfield, Cheshire, United Kingdom
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B. D. Alexander
4Duke University, Durham, North Carolina
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D. Andes
5University of Wisconsin, Madison, Wisconsin
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S. D. Brown
6The Clinical Microbiology Institute, Wilsonville, Oregon
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V. Chaturvedi
7New York State Department of Health, Albany, New York
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M. A. Ghannoum
8Case Western Reserve University, Cleveland, Ohio
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C. C. Knapp
9Trek Diagnostic Systems, Cleveland, Ohio
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D. J. Sheehan
10Pfizer, Inc., New York, New York
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T. J. Walsh
11National Cancer Institute, Bethesda, Maryland
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DOI: 10.1128/JCM.00566-08
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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.

  • Copyright © 2008 American Society for Microbiology
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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
M. A. Pfaller, D. J. Diekema, L. Ostrosky-Zeichner, J. H. Rex, B. D. Alexander, D. Andes, S. D. Brown, V. Chaturvedi, M. A. Ghannoum, C. C. Knapp, D. J. Sheehan, T. J. Walsh
Journal of Clinical Microbiology Aug 2008, 46 (8) 2620-2629; DOI: 10.1128/JCM.00566-08

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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
M. A. Pfaller, D. J. Diekema, L. Ostrosky-Zeichner, J. H. Rex, B. D. Alexander, D. Andes, S. D. Brown, V. Chaturvedi, M. A. Ghannoum, C. C. Knapp, D. J. Sheehan, T. J. Walsh
Journal of Clinical Microbiology Aug 2008, 46 (8) 2620-2629; DOI: 10.1128/JCM.00566-08
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KEYWORDS

antifungal agents
Candida
candidiasis

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