Journal article
Clinical breakpoints for the echinocandins and Candida revisited: Integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria
Drug resistance updates, Vol.14(3), pp.164-176
2011
DOI: 10.1016/j.drup.2011.01.004
PMID: 21353623
Abstract
The CLSI established clinical breakpoints (CBPs) for caspofungin (CSF), micafungin (MCF) and anidulafungin (ANF) versus Candida. The same CBP (susceptible (S): MIC
≤
2
mcg/ml; non-S: MIC
>
2
mcg/ml) was applied to all echinocandins and species. More data now allow reassessment of these CBPs.
We examined cases of echinocandin failure where both MICs and fks mutations were assessed; wild type (WT) MICs and epidemiological cutoff values (ECVs) for a large Candida collection; molecular analysis of fks hotspots for Candida with known MICs; and pharmacokinetic and pharmacodynamic (PK/PD) data. We applied these findings to propose new species-specific CBPs for echinocandins and Candida.
Of 18 candidiasis cases refractory to echinocandins and with fks mutations, 28% (CSF), 58% (ANF) and 66% (MCF) had MICs in the S category using CBP of ≤2
mcg/ml, while 0–8% would be S using CBP of ≤0.25
mcg/ml. WT MIC distributions revealed ECV ranges of 0.03–0.25
mcg/ml for all major species except
C. parapsilosis (1–4
mcg/ml) and
C. guilliermondii (4–16
mcg/ml). Among Candida tested for fks mutations, only 15.7–45.1% of 51 mutants were detected using the CBP for NS of >2
mcg/ml. In contrast, a cutoff of >0.25
mcg/ml for
C. albicans,
C. tropicalis,
C. krusei, and
C. dubliniensis detected 85.6% (MCF) to 95.2% (CSF) of 21 mutant strains. Likewise, a cutoff of >0.12
mcg/ml for ANF and CSF and of >0.06
mcg/ml for MCF detected 93% (ANF) to 97% (CSF, MCF) of 30 mutant strains of
C. glabrata. These data, combined with PK/PD considerations, support CBPs of ≤0.25
mcg/ml (S), 0.5
mcg/ml (I), ≥1 (R) for CSF/MCF/ANF and
C. albicans,
C. tropicalis and
C. krusei and ≤2
mcg/ml (S), 4
mcg/ml (I), and ≥8
mcg/ml (R) for these agents and
C. parapsilosis. The CBPs for ANF and CSF and
C. glabrata are ≤0.12
mcg/ml (S), 0.25
mcg/ml (I), and ≥0.5
mcg/ml (R), whereas those for MCF are ≤0.06
mcg/ml (S), 0.12
mcg/ml (I), and ≥0.25
mcg/ml (R).
New, species-specific CBPs for Candida and the echinocandins are more sensitive to detect emerging resistance associated with fks mutations, and better able to predict risk for clinical failure.
Details
- Title: Subtitle
- Clinical breakpoints for the echinocandins and Candida revisited: Integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria
- Creators
- M A Pfaller - University of Iowa, Iowa City, Iowa, United StatesD J Diekema - University of Iowa, Iowa City, Iowa, United StatesD Andes - University of Wisconsin, Madison, WI, United StatesM C Arendrup - Statens Serum Institute, Copenhagen, DenmarkS D Brown - The Clinical Microbiology Institute, Wilsonville, OR, United StatesS R Lockhart - Centers for Disease Control and Prevention, Atlanta, GA, United StatesM Motyl - Merck and Company, Inc, Rahway, New Jersey, United StatesD S Perlin - Public Health Research Institute, New Jersey Medical School–UMDNJ, Newark, NJ, United States
- Contributors
- CLSI Subcommittee for Antifungal Testing (Author)
- Resource Type
- Journal article
- Publication Details
- Drug resistance updates, Vol.14(3), pp.164-176
- DOI
- 10.1016/j.drup.2011.01.004
- PMID
- 21353623
- NLM abbreviation
- Drug Resist Updat
- ISSN
- 1368-7646
- eISSN
- 1532-2084
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 2011
- Academic Unit
- Epidemiology; Pathology; Internal Medicine
- Record Identifier
- 9983986262802771
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