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Correlation of MIC with Outcome for Candida Species Tested against Voriconazole: Analysis and Proposal for Interpretive Breakpoints
Open accessAbstract
Developing interpretive breakpoints for any given organism-drug combination requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic parameters, and the relationship between the in vitro activity and outcome from both in vivo and clinical studies. Using data generated by standardized broth microdilution and disk diffusion test methods, the Antifungal Susceptibility Subcommittee of the Clinical and Laboratory Standards Institute has now proposed interpretive breakpoints for voriconazole and Candida species. The MIC distribution for voriconazole was determined using a collection of 8,702 clinical isolates. The overall MIC 90 was 0.25 μg/ml and 99% of the isolates were inhibited at ≤1 μg/ml of voriconazole. Similar results were obtained for 1,681 Candida isolates (16 species) from the phase III clinical trials. Analysis of the available data for 249 patients from six phase III voriconazole clinical trials demonstrated a statistically significant correlation ( P = 0.021) between MIC and investigator end-of-treatment assessment of outcome. Consistent with parallel pharmacodynamic analyses, these data support the following MIC breakpoints for voriconazole and Candida species: susceptible (S), ≤1 μg/ml; susceptible dose dependent (SDD), 2 μg/ml; and resistant (R), ≥4 μg/ml. The corresponding disk test breakpoints are as follows: S, ≥17 mm; SDD, 14 to 16 mm; and R, ≤13 mm.
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“Analysis of this dataset demonstrated a strong relationship between AUC/MIC and outcome.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [150]
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“Therapeutic success was observed in approximately 80% of patients with a 24-hour AUC/MIC greater than 25, whereas when the AUC/MIC was less than 25, clinical failure was noted in 45% of patients.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [150]
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“Indeed, scatterplots of anidulafungin MICs (Fig. 3a) and micafungin MICs (Fig. 3b) versus caspofungin MICs show high levels of correlation ( R = 0.83), with 92% (anidulafungin) to 97% (micafungin) of all MICs for the two comparisons within ± 2 log 2 dilutions of one another (230).”
From Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem (2007) · cites this paper as [230]
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Metadata
- Authors
- Pfaller, M. A., Diekema, D. J., Rex, J. H., Espinel-Ingroff, A., Johnson, E. M., Andes, D., Chaturvedi, V., Ghannoum, M. A., Odds, F. C., Rinaldi, M. G., Sheehan, D. J., Troke, P., Walsh, T. J., & Warnock, D. W.
- Affiliations
- University of Iowa (US)
- AstraZeneca (United Kingdom) (GB)
- VCU Medical Center, Richmond, Virginia
- HPA Centre for Infections, Kingsdown, Bristol, United Kingdom
- University of Wisconsin–Madison (US)
- New York State Department of Health (US)
- Case Western Reserve University (US)
- University of Aberdeen (GB)
- The University of Texas at San Antonio Health Science Center (US)
- Pfizer (United States) (US)
- Pfizer (United Kingdom) (GB)
- National Institutes of Health (US)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Pfaller, M. A.
- ORCID
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2006-03
- Volume
- 44
- Issue
- 3
- Pages
- 819-826
- ISSN
- 0095-1137 (ISSN-L)
- 1098-660X
- PMC
- PMC1393146
- OpenAlex
- W2138433856
- Cited by
- 258
- References
- 43
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 12 · 2014: 8 · 2013: 5 · 2012: 16
- FWCI
- 25.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Microbiology (medical) › Bacterial Identification and Susceptibility Testing
- Keywords
- voriconazole, Candida species, interpretive breakpoints, minimum inhibitory concentration, antifungal susceptibility, MIC distribution, antifungal resistance
- MeSH terms
- Antifungal Agents, Candida, Candidiasis, Data Interpretation, Statistical, Humans, Microbial Sensitivity Tests, Pyrimidines, Triazoles, Fluconazole, Inhibitory Concentration 50, Endpoint Determination, Drug Resistance, Fungal, Voriconazole
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