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Purpose: Acute gastroenteritis caused by Salmonella spp. among children post a great threat for global public health. The increasing rate of drug-resistant Salmonella spp. has also become a challenging problem worldwide. In this study, the prevalence, serotypes, and antimicrobial characteristics of Salmonella isolated from children in Guangzhou, China, were investigated to provide supporting information for clinical treatment and prevention. Methods: Clinical data of children featured with gastroenteritis symptoms from 2018 to 2023 in Guangdong Women and Children Hospital were collected. The difference and fluctuation of antimicrobial resistance between serotypes and years were retrospectively analyzed. Results: A total of 1304 Salmonella isolates were cultural-confirmed. The overall positive rate of Salmonella isolated from stool samples was 22.0% (1304/5924). Salmonella infections occur mainly from June to September and the majority of infected children aged under 4 years. Serogroup B was the most common serogroup among Salmonella isolates (74.6%, 973/1304). The predominant serotypes of Salmonella isolates were Typhimurium (63.1%, 823/1304). Higher drug resistance rate of Salmonella spp. to ceftriaxone was observed in 2023. The drug resistance rates of Salmonella isolates to sulfamethoxazole/trimethoprim and ampicillin are at high level during the past 6 years. Notably, higher multi-drug resistance (MDR) rate was demonstrated in Salmonella Typhimurium compared with other serotypes. Conclusion: Salmonella Typhimurium was the most common serotype isolated from children in Guangzhou, China, and it may mainly account for the high drug resistance rate in Salmonella spp. to most of the antimicrobial profiles. For controlling the high drug resistance rate of Salmonella spp. continuous surveillance of drug resistance and appropriate use of antibiotics based on clinical and laboratory results are of great significance. [ABSTRACT FROM AUTHOR]