Impact of Colistin Risk-Management Measures on Resistance in Escherichia coli from Pigs in Japan and Genomic Characteristics of mcr-1-Carrying Plasmids

Background/Objectives: Colistin, previously of limited clinical relevance in human medicine, has become one of the last-line antimicrobials for infections caused by multidrug-resistant Gram-negative bacteria and was classified by the World Health Organization as a highest-priority critically important antimicrobial (HPCIA) in 2017. In Japan, based on a risk assessment, risk-management measures for colistin were strengthened in 2018 by revoking its designation as a feed additive and restricting its veterinary medicinal use to second-line treatment. This study evaluated changes in colistin sales volume and resistance among Escherichia coli from pigs and characterized mcr-1-carrying isolates. Methods: A total of 2212 E. coli isolates collected through the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) from healthy pigs at slaughterhouses (n = 1122) and diseased pigs submitted for pathological inspection (n = 1090) during 2013–2023 were subjected to antimicrobial susceptibility tests. Isolates with colistin minimum inhibitory concentrations of at least 4 μg/mL were screened for mcr-1 to mcr-10. Long-read whole-genome sequencing was performed for 32 mcr-1-positive isolates. Results: Colistin resistance rate among isolates from diseased pigs decreased from 52.0% in 2017 to 7.7% in 2023, whereas resistance among isolates from healthy pigs remained at or below 6.0% throughout the study period. mcr-1 was the predominant mobile colistin resistance gene. ST88, ST100, and ST1 were the predominant sequence types among isolates from diseased pigs, whereas healthy-pig isolates exhibited greater sequence-type diversity. IncI2 was the dominant mcr-1 plasmid type, and all IncI2 plasmids were predicted to be conjugative. Their backbones were highly similar to pHNSHP45, an IncI2 plasmid identified in an E. coli isolate collected from a pig in China in 2013, retained pil and tra/vir regions, and generally lacked ISApl1. Conclusions: The strengthening of risk-management measures in 2018 was followed by a substantial decline in colistin resistance rate among isolates from diseased pigs, supporting the effectiveness of these measures. Stable and potentially transmissible IncI2 plasmids continue to maintain mcr-1, underscoring the importance of maintaining these risk-management measures, ensuring prudent antimicrobial use, and continuing integrated phenotypic and genomic surveillance.