Antimicrobial agents have been used in meat production for decades and its consumption is considered an key driver for the emergence and dissemination of antimicrobial resistance (AMR). However, large-scale studies on AMR changes in animal isolates since the introduction of antimicrobial usage remain scarce. We applied whole genome sequencing analysis to 982 animal-derived Escherichia coli collected in China from 1970s to 2019 and found increasing trends for the presence of numerous antimicrobial resistance genes (ARGs), including those conferring resistance to critically important agents for veterinary ( orfenicol and nor oxacin) and human medicine (colistin, cephalosporins, and meropenem). Extensive diversity and increasing complexity of ARGs and their associated mobile genetic elements (MGEs) such as plasmids were also observed. The plasmids, IncC, IncHI2, IncK, IncI, IncX and IncF played a key role as highly effective vehicles for disseminating ARGs. Correlation analysis also revealed an association between antimicrobial production and emergence of ARGs at a spatial and temporal level. Prohibiting or strictly curtailing antimicrobial use in animals will potentially negate the current trends of AMR as the bacterial genome is highly changeable and using different drugs of the same class, or even unrelated classes, may co-select for MGEs carrying a plethora of co-existing ARGs. Therefore, limiting or ceasing antimicrobial use in animals to control AMR requires careful consideration.

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China Antimicrobial Resistance Surveillance Network for Pets (CARPet) was established in 2021 to monitor the resistance profiles of clinical bacterial pathogens from companion animals. From 2018 to 2021, we recovered and tested 4,541 isolates from dogs and cats across 25 Chinese provinces, with Escherichia coli (18.5%) and Staphylococcus pseudintermedius (17.8%) being the most predominant bacterial species. The Enterobacterales were highly susceptible to tigecycline, meropenem, colistin, and amikacin (70.3%–100.0%), but showed moderate resistance to ampicillin, ceftriaxone, doxycycline, florfenicol, levofloxacin, enrofloxacin, and trimethoprim-sulfamethoxazole (29.3%–56.7%). About 66.3% of Acinetobacter spp. were resistant to florfenicol, with relatively low resistance to another 11 antibiotics (1.2%–23.3%). The Pseudomonas spp. showed high susceptibility to colistin (91.7%) and meropenem (88.3%). The coagulase-positive Staphylococcus spp. showed higher resistance rates to most antimicrobial agents than coagulase-negative Staphylococcus isolates. However, over 90.0% of Staphylococcus spp. were susceptible to linezolid, daptomycin and rifampin, and no vancomycin-resistant isolates were detected. E. faecium isolates demonstrated higher resistance rates to most antimicrobial agents than E. faecalis isolates. Streptococcus spp. isolates showed low resistance to most antimicrobial agents except for doxycycline (78.2%) and azithromycin (68.8%). Overall, the tested clinical isolates showed high rates of resistance to commonly used antimicrobial agents in companion animals. Therefore, it is crucial to strengthen the monitoring of bacterial resistance in pets. By timely and effectively collecting, analyzing, and reporting antimicrobial resistance dynamics in pets, the CARPet network will become a powerful platform to provide scientific guidance for both pet medical care and public health.