DOI: 10.1101/19006106Nov 29, 2019Paper

Using the Association Between Antibiotic Susceptibility and Genetic Relatedness to Rescue Old Drugs for Empiric Use

MedRxiv : the Preprint Server for Health Sciences
Derek R MacFaddenWilliam P Hanage


Background: Rising rates of antibiotic resistance have led to the use of broader spectrum antibiotics and increasingly compromise empiric therapy. Knowing the antibiotic susceptibility of a pathogens close genetic relative(s) may improve empiric antibiotic selection. Methods: Using genomic and phenotypic data from three separate clinically-derived databases of Escherichia coli isolates, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate prediction of antibiotic susceptibility to common antibiotics. Results: We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010-2018. The most common sequence type (ST) was ST131 (30%). Antibiotic susceptibility to ciprofloxacin and trimethoprim-sulfamethoxazole were lowest (<=72%). Across all approaches, model performance (AUC) ranges for predicting antibiotic susceptibility were greatest for ciprofloxacin (0.76-0.97), and lowest for trimethoprim-sulfamethox...Continue Reading

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