Quantitative Release Assessment of <i>mcr</i>-mediated Colistin-resistant <i>Escherichia Coli</i> from Japanese Pigs

Abstract

Colistin is a critically important antibiotic for humans. The Japanese government withdrew colistin growth promoter and shifted therapeutic colistin to a second-choice drug for pigs in 2017. A quantitative release assessment of <i>mcr</i>-mediated colistin-resistant <i>Escherichia coli</i> (<i>E. coli</i>) in Japanese finisher pigs was conducted under the World Organisation for Animal Health (OIE) risk assessment framework. Input data included colistin resistance and <i>mcr-1-5</i> test results for <i>E. coli</i> isolates in the Japan Veterinary Resistance Monitoring System (JVARM), postal survey results regarding indication disease occurrence and colistin use by swine veterinarians in 2017 and 2018, and colistin resistance and <i>mcr</i> monitoring experiments at four pig farms in 2017-2018. An individual-based model was developed to assess the risk: the proportion of Japanese finisher pigs with <i>mcr-1-5</i>-mediated colistin-resistant <i>E. coli</i> dominant in the gut on an arbitrary day. Before implementing risk management measures, the risk was estimated to be 5.5% (95% CI: 4.2%-10.1%). At 12 months after stopping colistin growth promoter, the proportion of pigs with plasmid-mediated colistin-resistant <i>E. coli</i> declined by 52.5% on the experiment farms (95% CI: 8.7%-80.8%). The probability of therapeutic colistin use at the occurrence of bacterial diarrhea declined from 37.3% (95% CI: 30.3%-42.5%) in 2017 to 31.4% (95% CI: 26.1%-36.9%), and that of edema disease declined from 55.0% (95% CI: 46.0%-63.7%) to 44.4% (95% CI: 36.9%-52.0%). After risk management implementation, the risk was estimated to have declined to 2.3% (95% CI: 1.8%-4.3%; 58.2% reduction). Scenario analyses showed that pen-level colistin treatment effectively reduces the risk from 5.5% to 4.7% (14.5% reduction), an effect similar to stoppage of therapeutic colistin (16.4% reduction to 4.6%).