DOI: 10.1101/511402Jan 7, 2019Paper

Reconciling the potentially irreconcilable? Genotypic and phenotypic amoxicillin-clavulanate resistance in Escherichia coli

BioRxiv : the Preprint Server for Biology
Timothy J DaviesA. Sarah Walker


Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 E. coli bloodstream infection isolates from Oxfordshire, UK, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity 23% (78/339)) but improved when genetic features associated with penicillinase hyper-production (e.g. promoter mutations, copy number estimates) were considered (sensitivity 82% (277/339); p<0.0001). Most discrepancies occurred in isolates with peri-breakpoint MICs. We investigated two potential causes; the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulan...Continue Reading

Related Concepts

Bipolar Disorder
Disease Susceptibility
Escherichia coli
Amoxicillin / Clavulanate
Agar Dilution Method
Phenotype Determination
Inhibitory Synapse
Resistance Process

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