MASTER: a model to improve and standardize clinical breakpoints for antimicrobial susceptibility testing using forecast probabilities

• Published in: Journal of antimicrobial chemotherapy 2017-09, Vol.72 (9), p.2553-2561
• Main Authors: Blöchliger, Nicolas, Keller, Peter M, Böttger, Erik C, Hombach, Michael
• Format: Article
• Language: English
• Subjects: Ampicillin - pharmacology; Anti-Bacterial Agents - pharmacology; Escherichia coli - drug effects; Escherichia coli Infections - microbiology; Humans; Microbial Sensitivity Tests - methods; Microbial Sensitivity Tests - standards; Models, Theoretical; Probability
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkx196

The procedure for setting clinical breakpoints (CBPs) for antimicrobial susceptibility has been poorly standardized with respect to population data, pharmacokinetic parameters and clinical outcome. Tools to standardize CBP setting could result in improved antibiogram forecast probabilities. We propose a model to estimate probabilities for methodological categorization errors and defined zones of methodological uncertainty (ZMUs), i.e. ranges of zone diameters that cannot reliably be classified. The impact of ZMUs on methodological error rates was used for CBP optimization. The model distinguishes theoretical true inhibition zone diameters from observed diameters, which suffer from methodological variation. True diameter distributions are described with a normal mixture model. The model was fitted to observed inhibition zone diameters of clinical Escherichia coli strains. Repeated measurements for a quality control strain were used to quantify methodological variation. For 9 of 13 antibiotics analysed, our model predicted error rates of  0.1% for ampicillin, cefoxitin, cefuroxime and amoxicillin/clavulanic acid. Increasing the susceptible CBP (cefoxitin) and introducing ZMUs (ampicillin, cefuroxime, amoxicillin/clavulanic acid) decreased error rates to