Salmonella is a rod-shaped, gram-negative bacterium with no capsule and spore and is a member of the Enterobacterales (1). It can be transmitted via contaminated food products including meat, beef, potatoes and cucumbers, which may lead to foodborne outbreaks, and results in about 23,000 deaths every year (2–4). Moreover, Salmonella is the main pathogenic cause of diarrhea in children, with the largest proportion of infections in pediatric patients < 5 years old and most commonly occurs between summer and autumn (5, 6). Currently, more than 2,500 Salmonella serotypes have been reported and among them, over 20 serotypes can cause zoonotic diseases (7). S. typhimurium and S. enteritidis are the major Salmonella serotypes responsible for gastroenteritis and diarrhea in both children and adults (8).

The pathogenicity of Salmonella is mainly related to its toxic factors, including pathogenic islands, toxic plasmids, pili and enterotoxins (9, 10). Different serotypes carrying different virulence genes can exhibit different sensitivity to antibiotics (11). In recent years, studies have shown that Salmonella antibiotic resistance has markedly increased, due to long-term antibiotic use in the poultry industry and animal laboratory products (12, 13). Furthermore, there are many contraindications to clinical medication for children, which brings great challenges to clinical diagnosis and treatment. In order to understand Salmonella serotype distribution and antimicrobial resistance in Guangzhou, Southern China and to identify potential control strategies for formulating prevention and treatment plans, a retrospective study of 1,338 Salmonella strains isolated in Guangzhou Women and Children's Medical Center (National Children's Medical Center for South Central Region) from 2016 to 2021 was conducted in this study.

Salmonella is a zoonotic intestinal pathogen with many serotypes, mainly causing food-borne infections which lead to corresponding clinical symptoms (15). Salmonella infections are primarily divided into typhoidal and non-typhoidal (16). The former manifests as bloodstream infections, which are more common in adults; While the latter usually manifests as intestinal infections, which cause symptoms such as diarrhea, fever and abdominal pain and are more common in children (17, 18). This study demonstrated that the main specimen type of children with Salmonella infection was feces (92.75%), and fecal Salmonella isolation rate was increasing year by year, mainly in infants and toddlers under 3 years old (92.97%), consistent with domestic reports (19). This may be related to the fact that children are more susceptible than adults due to their lower immunity and weak gastrointestinal resistance (20). On the other hand, infant milk products have been reported as related to Salmonella outbreaks worldwide (21). This study also showed that Salmonella infections in children tend to have a high incidence in summer and autumn, which was consistent with domestic reports (22). However, the winter Salmonella infection rate in Guangzhou is still relatively high compared with that in northern China. This may be related to the geographical location of Guangzhou, which has a south subtropical maritime monsoon climate, with an average annual temperature of 21.5–22.2°C and abundant rainwater resources. Hot and humid weather promotes the growth of Salmonella and insufficient heat treatment of food can increase the risk of Salmonella infection.

In this study, we conducted a study of the clinical manifestations of Salmonella infection in children. 1,338 children with intestinal Salmonella infection had fever (62.18%) and diarrhea (60.16%) as prominent symptoms, but some children did not present with gastrointestinal symptoms. Previous reports of domestic Salmonella invasive infections mainly concentrated on typhoid or paratyphoid bloodstream infections (23, 24). In recent years, improvements in living standards and sanitation facilities have maintained Salmonella typhoid and paratyphoid infections at a low level. The increase in detection rate of invasive non-typhoid Salmonella (iNTS) has gradually attracted attention. The main diagnosis of invasive Salmonella infection is based on systemic multi-system clinical manifestations, symptoms of infection and poisoning, and Salmonella cultured in sterile body fluids (25). Extraintestinal infections caused by iNTS have also been reported, and the clinical features are similar to those of typhoid fever. It usually does not cause diarrhea, but causes bloodstream infections (such as bacteremia) or secondary systemic focal infections (such as meningitis), and failure to treat can often lead to death. The main reported serotypes are typhimurium, enteritidis, dublin and swine cholera. S. typhimurium ST313 is the main epidemic type of iNTS internationally, especially in Africa (26, 27). Specific susceptible populations of iNTS include HIV patients, immunodeficiency, hematological malignancies, young children, and malnourished or anemic adolescents, with a fatality rate as high as 20% (28). Unlike common NTS infections, patients rarely displayed gastroenteritis symptoms, but all had fever symptoms. Combined with the gradual increase in detection rate of Salmonella in recent years, the trend of increasing iNTS in Guangzhou cannot be ruled out. In addition, this study showed that there some children experienced diarrhea with clinical manifestations similar to viral diarrhea, no symptoms of high fever and diarrhea, routine stool microscopy, a significant increase in the number of stools, accompanied by obvious electrolyte metabolism disorders, and fecal culture detects Salmonella positive. Therefore, the necessity of early fecal culture detection in the diagnosis and treatment of children with diarrhea should be emphasized to avoid misdiagnosis.

The serotypes of 1,338 Salmonella strains in this study covered groups A to E, mainly group B (1110, 82.88%) and group D (124, 9.27%), of which S. typhimurium had the highest detection rate (1053, 78.69%), followed by S. enteritidis (7.17%) and S. neurangium (2.17%). The detection rate of S. typhimurium was higher than that reported by the CHINET Bacterial Resistance Surveillance Network (27.4%), and also higher than that of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology (51.6%) and the Affiliated Children's Hospital to Zhengzhou University (36.5%) (29, 30). In addition, the serotypes detected in this study were different to serotypes collected in Wuhan, Beijing, Zhengzhou and other locations, indicative of regional differences in Salmonella serotypes. A total of 48 serotypes were detected in this study and the distribution was diversified, with some rare serotypes. Different Salmonella serotypes exhibit differences in antibiotic resistance. AMP resistance was mainly manifested in Salmonella typhimurium, enteritidis, indiana and delby as AMP was the earliest and most widely used antibiotic in livestock in China (31). The diversification of serotype distribution will lead to broadening of the MDR phenotype and antimicrobial resistance spectrum, and the trend of pan-drug resistance will become more evident. In previous studies, MDR strains mainly existed in S. typhimurium, but this study demonstrated that S. typhimurium had the lowest MDR rate among MDR Salmonella. Therefore, it is necessary to continuously and regularly monitor Salmonella serotypes in children to detect changes in the main types as early as possible.

Due to the excessive use of antibiotics in animal husbandry and clinical practice, Salmonella resistance is increasing, especially to AMP and 3rd generation cephalosporins (32). Generally, Salmonella has been resistant to previously used first-line antimicrobial drugs such as AMP, CHL, sulfamethoxazole, and amoxicillin. In this study, Salmonella presented the highest resistance rate against AMP of 84.5%, which was greater than other domestic scholars and regions to AMP. The resistance rate to 3rd generation cephalosporins (CRO, CTX, CAZ) was about 40.0%. Salmonella mainly produces ESBL, extended-spectrum β-lactamase and AmpC enzymes to generate resistance to cephalosporin antimicrobial drugs. Synthesis of Salmonella ESBL will indirectly reduce its sensitivity to quinolones, leading to the generation of multi-drug resistant strains resistant to cephalosporins and quinolones (33). Although the antimicrobial resistance rate of CIP in this study was low (6.7%), due to the side effects of central nervous and joint toxicity, it is no longer a suitable drug for children with Salmonella infection. CLSI 2020 recommends that only AMP, quinolones and trimethoprim-sulfamethoxazole are required for regular reports for fecal-isolated Salmonella. According to the antimicrobial sensitivity results of this study and the poor therapeutic effect of AMP in clinical use for S. Typhimurium, AMP is unsuitable for clinical promotion and application. At present, Salmonella still maintains high sensitivity to enzyme inhibitor compound preparations, 4th generation cephalosporins and IPM. When choosing antimicrobial treatment, drugs with antibacterial activity against Salmonella should be selected. Antimicrobial spectrum does not include gastrointestinal infections and drugs with unknown antimicrobial activity against Salmonella may lead to drug resistance. In order to decrease antibiotic consumption and AMR, the majority of gastroenteritis caused by Salmonella should not be treated with antibiotics (23, 34). In general, the current resistance rate of 3rd generation cephalosporins and quinolone antibiotics is still low, but there is an upward trend. Antimicrobial susceptibility studies to azithromycin are lacking.

There have been disagreements regarding the selection, use, and timing of antibiotics for Salmonella infection in children (35). At present, most of the 3rd generation cephalosporins are the first choice for clinical use, with azithromycin as an alternative. Quinolone antibiotics are generally not recommended for children, but can be considered for severe infections when no other antibiotics can be substituted. For MDR Salmonella, carbapenem antibiotics are suggested. The use of multiple antibiotics in combination is not recommended, and specific antibiotic selection should be based on the local epidemiology and antimicrobial susceptibility results. recommended course of treatment for intestinal infections is within 1 week, while the course of treatment for extra-intestinal infections needs to be extended. It is worth noting that there are few studies with large samples on the comparison of treatment effects between azithromycin, 3rd generation cephalosporins and quinolone antibiotics in children's NTS, and more extensive and in-depth research is required.

In summary, under the current pressure of antibiotic selection, the typing and continuous monitoring of antimicrobial resistance of intestinal Salmonella is important research work to provide clear epidemiological evidence for clinical diagnosis, treatment, and prevention of infection.