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

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

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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, …

Journal of clinical microbiology, Vol.46(8), pp.2620-2629

08/2008

DOI: 10.1128/JCM.00566-08

PMCID: PMC2519503

PMID: 18579718

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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 < or = 2 microg/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 microg/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 microg/ml. The clinical data set included only three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were > 2 microg/ml (two C. parapsilosis isolates at 4 microg/ml and one C. rugosa isolate at 8 microg/ml). Based on these data, the CLSI subcommittee has decided to recommend a "susceptible only" breakpoint MIC of < or = 2 microg/ml due to the lack of echinocandin resistance in the population of Candida isolates thus far. Isolates for which MICs exceed 2 microg/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.

Antifungal Agents - pharmacology

Lipoproteins - therapeutic use

Humans

Treatment Outcome

Clinical Trials as Topic

Statistics as Topic

Candidiasis - microbiology

Candida - isolation & purification

Antifungal Agents - therapeutic use

Microbial Sensitivity Tests

Candidiasis - drug therapy

Lipoproteins - pharmacology

Echinocandins - therapeutic use

Candida - drug effects

Drug Resistance, Fungal

Lipopeptides

Echinocandins - pharmacology

Details

Title: Subtitle: Correlation of MIC with outcome for Candida species tested against caspofungin, anidulafungin, and micafungin: analysis and proposal for interpretive MIC breakpoints
Creators: M A Pfaller - University of Iowa, Pathology
D J Diekema
L Ostrosky-Zeichner
J H Rex
B D Alexander - Duke University
D Andes
S D Brown
V Chaturvedi
M A Ghannoum
C C Knapp
D J Sheehan
T J Walsh
Resource Type: Journal article
Publication Details: Journal of clinical microbiology, Vol.46(8), pp.2620-2629
DOI: 10.1128/JCM.00566-08
PMID: 18579718
PMCID: PMC2519503
NLM abbreviation: J Clin Microbiol
ISSN: 0095-1137
eISSN: 1098-660X
Publisher: United States
Language: English
Date published: 08/2008
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Internal Medicine
Record Identifier: 9983986369002771

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