MASTER: a model to improve and standardize clinical breakpoints for antimicrobial susceptibility testing using
Nicolas Blöchliger1, Peter M Keller1, Erik C Böttger1
1Institute of Medical Microbiology, University of Zurich, Gloriastrasse 30/32, 8006 Zürich, Switzerland.
The Journal of Antimicrobial Chemotherapy
|September 2, 2017
Summary
A new model standardizes antimicrobial susceptibility testing by optimizing clinical breakpoints (CBPs) and introducing zones of methodological uncertainty (ZMUs). This approach minimizes errors, improving the reliability of antibiotic susceptibility interpretations.
Area of Science:
- Microbiology
- Clinical Pharmacology
- Statistical Modeling
Background:
- Clinical breakpoint (CBP) setting for antimicrobial susceptibility testing lacks standardization, impacting antibiogram accuracy.
- Methodological variations in population data, pharmacokinetics, and clinical outcomes affect CBP reliability.
- Standardized tools are needed to improve antibiogram forecast probabilities and clinical decision-making.
Purpose of the Study:
- To develop and validate a model for standardizing clinical breakpoint setting.
- To estimate probabilities of methodological categorization errors and define zones of methodological uncertainty (ZMUs).
- To optimize CBPs by assessing the impact of ZMUs on error rates.
Main Methods:
- A statistical model was developed to differentiate theoretical true inhibition zone diameters from observed diameters affected by methodological variation.
- Normal mixture models described true diameter distributions, fitted to observed inhibition zone diameters of clinical Escherichia coli strains.
- Methodological variation was quantified using repeated measurements from a quality control strain.
Main Results:
- The model predicted error rates below 0.1% for 9 of 13 antibiotics using current EUCAST CBPs.
- Error rates exceeded 0.1% for ampicillin, cefoxitin, cefuroxime, and amoxicillin/clavulanic acid.
- Adjusting CBPs and implementing ZMUs reduced error rates, though one ZMU was deemed impractical due to a high isolate proportion (41%).
Conclusions:
- Clinical breakpoints can be improved and standardized by minimizing methodological categorization errors.
- Zones of methodological uncertainty (ZMUs) can be implemented when intermediate zones are not suitable for PK/PD or dosing.
- Optimized CBPs will enhance standardized interpretation of antibiotic susceptibility testing at a defined probability level.
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