Non-typhoidal Salmonella is one of the predominant pathogens responsible for foodborne gastroenteritis globally, and antimicrobial resistance in this pathogen poses a growing threat to clinical treatment. Long-term systematic surveillance of serotype dynamics and resistance trends is essential for guiding targeted prevention and antimicrobial stewardship in China. In this study, a total of 8778 Salmonella strains were isolated from sporadic diarrheal patients in 11 prefecture-level cities of Zhejiang Province, China, spanning the period from 2019 to 2025. The isolates were subjected to serotype identification and antimicrobial susceptibility testing. The temporal trend of MDR was evaluated using the Cochran-Armitage trend test. Observed-to-expected (O/E) ratio analysis was applied to assess the geographical association between Salmonella serotypes and urban distribution. From 2019 to 2024, S . Typhimurium, S . Enteritidis, and S . London consistently dominated as the three predominant serotypes. However, a marked shift in the epidemic structure was observed in 2025, with monophasic S . Typhimurium surging to the leading position (24.75%). Annual serotype richness ranged from 55 to 141 serotypes, and both the Shannon and Simpson exhibited a continuous upward trend. Geographical aggregation characteristics were identified in specific serotypes. Hangzhou exhibited the most pronounced enrichment of monophasic S . Typhimurium (O/E = 4.62). Zhoushan harbored the strongest enrichment for S . Newport (O/E = 3.89), while Quzhou displayed notable enrichment of S . Give (O/E = 3.03). Overall resistance to ampicillin and tetracycline remained high (68.1% and 60.2% in 2025, respectively), while resistance to chloramphenicol and co-trimoxazole rose steadily. Distinct serotype-specific antimicrobial resistance profiles were observed among prevalent strains. Specifically, S . Typhimurium exhibited high-level co-resistance to aminoglycosides and sulfonamides. S . Enteritidis was characterized by predominant resistance to β-lactam/β-lactamase inhibitor combinations and cephalosporins. S . London and S . Thompson displayed prominent macrolide resistance, while S . Kentucky was distinguished by severe fluoroquinolone resistance. The overall MDR rate of all isolates was 65.8%, and statistical analysis confirmed a statistically significant increasing temporal trend in MDR (r = 0.1181, P = 4.89 × 10⁻²⁴). In summary, the findings underscore the urgent need for integrated serotype-and-resistance surveillance, strengthened food-chain source control, and optimized clinical antimicrobial stewardship within a One Health framework. Clinical trial number: Not applicable.
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