Prevalence of Third-Generation Cephalosporin-Resistant Salmonella in Animals in China: the Key Role of ESBL, AmpC, and Other Β-Lactamase Strains in the Genome.

OBJECTIVE:To elucidate the drug resistance characteristics, epidemiological distribution, and molecular mechanisms of third-generation cephalosporin-resistant Salmonella from animal sources in China during 2016-2024. METHODS:Antimicrobial susceptibility testing, serotyping, and whole-genome sequencing (WGS) were employed. RESULTS:Salmonella exhibited the highest resistance rate to ampicillin (91.9%), followed by sulfisoxazole (87.4%) and tetracycline (83.1%). Among these, strains producing extended-spectrum β-lactamases (ESBLs) accounted for 67.1% and were widely prevalent in chickens and ducks; their dominant resistance gene, blaCTX-M-55, is closely associated with IncI2 and is co-driven by ISEcp1, ISKpn26, IS150, and IS103. 6.2% of the strains carried cephalosporinases (AmpC), primarily from chickens, with blaCMY-59 associated with ISEcp1 as the predominant genotype. An additional 27.1% carried other β-lactamases, mostly from pigs, with the predominant genotype being blaTEM-1 associated with IS406. Notably, the carbapenemase gene blaNDM-1/5 was detected only in strains producing other β-lactamases and was associated with ISSbol and ISRor2. Serotype distribution showed that S. Kentucky predominantly carried ESBLs and AmpC, while S. Enteritidis was dominated by other β-lactamases. Phylogenetic analysis revealed that serotype is the primary factor determining the structure of Salmonella clonal groups, and the acquisition of resistance to third-generation cephalosporins in Salmonella may depend on both clonal transmission and horizontal gene transfer. CONCLUSION:This study is the first to untangle the differences in animal distribution and serotype associations of third-generation cephalosporin-resistant Salmonella over the past decade and to elucidate, at the genomic level, the formation mechanisms and transmission pathways underlying different resistance phenotypes.