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 mcr-mediated colistin-resistant Escherichia coli (E. coli) in Japanese finisher pigs was conducted under the World Organisation for Animal Health (OIE) risk assessment framework. Input data included colistin resistance and mcr-1-5 test results for E. coli 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 mcr 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 mcr-1-5-mediated colistin-resistant E. coli 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 E. coli 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%).
Highlights
Colistin is a critically important antibiotic called an antibiotic of last resort1) in light of the rapid global rise of multi-drug-resistant Enterobacteriaceae
The mcr gene, which is harbored on a plasmid, can be transmitted between bacteria, which poses a significant threat to humans, as important Enterobacteriaceae pathogens such as multi-drugresistant Pseudomonas aeruginosa (MDRP), multi-drugresistant Acinetobacter (MDRA), and carbapenem-resistant Enterobacteriaceae (CRE) can acquire colistin resistance as well
The objectives of this study were to quantitatively assess the current risk of producing finisher pigs harboring mcrmediated colistin-resistant Escherichia coli (E. coli) at farms just before sending the animals to the slaughterhouse and estimate the effects of potential control measures, including those already implemented via the risk management measures instituted by the MAFF
Summary
Colistin is a critically important antibiotic called an antibiotic of last resort1) in light of the rapid global rise of multi-drug-resistant Enterobacteriaceae. The use of injection formulas, which had been suspended due to the frequent adverse effects such as renal dysfunction, was re-approved in 2015 in response to the global rise of multi-drug-resistant gram negative bacterial infections[3]). Prior to 2015, when a mobile colistinresistance gene, mcr-1, was reported in China5), this was the only known mechanism of colistin resistance. The mcr gene, which is harbored on a plasmid, can be transmitted between bacteria, which poses a significant threat to humans, as important Enterobacteriaceae pathogens such as multi-drugresistant Pseudomonas aeruginosa (MDRP), multi-drugresistant Acinetobacter (MDRA), and carbapenem-resistant Enterobacteriaceae (CRE) can acquire colistin resistance as well. In Japan, a high prevalence of mcr-1 (30.0%), -3 (8.3%), and -5 (28.3%) was reported among 120 isolates from diseased pigs11), and a low proportion (1.9%, 39/2052 isolates) of mcr-1 and the absence of mcr-2 was reported among healthy pigs[2])
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