Analysis of foodborne salmonellosis serotypes and drug resistance in children in Chenzhou City of China from 2017 through 2022

Introduction

Salmonella is a non-capsulated, non-spore-forming, facultative anaerobic gram-negative rod. Most members of the Salmonella genus do not ferment lactose, and this characteristic is used for the isolation culture and identification of Salmonella (1). Salmonella is ubiquitous in nature and often resides in human and animal intestinal tracts. Salmonella is primarily transmitted via the fecal-oral route, and does not degrade protein, produce indoles, or cause sensory changes to food after contamination. Salmonella is one of the most common pathogens in bacterial foodborne illness (2) and can infect humans and animals. After humans are infected with Salmonella, the common symptoms include diarrhea, fever, stomach spasms and nausea, vomiting, and headache. Data from a previous study revealed that children below the age of five, immunocompromised individuals, and the elderly are susceptible to Salmonella (3). Self-limiting gastroenteritis is the most common presentation of salmonellosis in children; however, an invasive infection may occur in severe cases, and this may be accompanied by meningitis, arthritis, and osteomyelitis that may even be life threatening (4,5). Intestinal infection caused by Salmonella is a significant global public health issue, and the annual death toll due to salmonellosis is 155,000 people (6). Infectious diarrhea caused by Salmonella is a common health problem for children and is the leading cause of death in children below 5 years of age (7). In 2021, the World Health Organization reported that Salmonella caused 500 million infections worldwide, of which more than 200 million occurred in children [https://www.who.int/news-room/fact-sheets/detail/salmonella-(non-typhoidal)].

There are regional differences in the composition and dominance of Salmonella serotypes. A global survey of human Salmonella outbreaks conducted at the beginning of this century revealed that S. Enteritidis was the most common serotype, followed by Salmonella Typhimurium (S. Typhimurium) (8). In 2019, the top five Salmonella serotypes isolated in Europe were Salmonella Infantis (S. Infantis), Salmonella Enteritidis (S. Enteritidis), Salmonella enterica serovar Typhimurium monophasic variant (S. Typhimurium 1,4,[5],12:i-), S. Typhimurium, and Salmonella Derby (S. Derby) (9). The principal foodborne pathogen in the United States of America is Salmonella and mainly includes the following four serotypes: S. Enteritidis, Salmonella Newport (S. Newport), S. Typhimurium, and Salmonella Javiana (S. Javiana) (10). From 2016 to 2017, S. enterica serovar I 4,[5],12:i:-, S. Enteritidis and, Salmonella Bareilly (S. Bareilly) were also the most common Salmonella serotypes in patients with diarrhea and foodborne illnesses in South Korea (11). There are very few extant studies on salmonellosis in children in China; however, the results of an epidemiologic survey have shown differences between the Salmonella serotypes isolated from children and those isolated from adults (12). In addition, research has shown that after children were infected with Salmonella, the possibility of hospitalization was higher and the antibiotic treatment duration was longer for patients who were younger (13).

Antibiotics constitute the principal treatment for salmonellosis. However, the unregulated use of antibiotics in clinical practice and widespread use of antibiotics in animal husbandry has worsened antibiotic resistance in Salmonella, causing an increase in multidrug resistance (MDR) and the drug-resistance spectrum. As an important foodborne pathogen, the issue of Salmonella resistance has become a global public health issue (14). In 2021, the European Food Safety Authority published a report (15) stating that the drug-resistance rates of Salmonella in human stool samples to sulfonamides, ampicillin (AMP), and tetracycline (TET) were 29.0%, 25.8%, and 25.6%, respectively. The results of a survey of five Chinese provinces showed that the drug-resistance rates of Salmonella to nalidixic acid (NAL) and sulfafurazole were 64% and 59%, respectively, and the MDR rate was 53.4% (16). In addition to drug resistance to traditional antibiotics, strains that are resistant to 3^rd-generation cephalosporins, ciprofloxacin (CIP), and azithromycin (AZI) have continued to emerge in recent years (17), and the prevalence of these strains poses a severe threat to general public health safety and the health of minors particularly.

Thus, the analysis of the serotype-distribution characteristics and drug-resistance patterns of salmonella in children has important value in anti-infective treatment and the implementation of public health surveillance. This study was conducted to determine the distributional status and drug-resistance characteristics of foodborne salmonellosis in children and to curb the unnecessary use of antibiotics. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-120/rc).

Methods

Sample sources

To test for Salmonella, stool/anal swab samples were collected from patients under 18 years of age who with a chief complaint of diarrhea (≥3 episodes of diarrhea per day), or abnormal stools, and who were treated at two sentinel hospitals, Chenzhou No. 1 and No. 4 People’s Hospital. Both hospitals are affiliated hospitals of Xiangnan University. These two hospitals are public tertiary comprehensive hospitals, covering approximately 6–7 million people throughout Chenzhou and surrounding areas from 2017 through 2022, and over the past 6 years, a total of 3,118 cases of diarrhea were monitored, including 1,263 cases of childhood diarrhea. We obtained general information, including their age, sex, and season of onset, from the inpatient and outpatient health records of the hospitals. A study reported that the infection rate of Salmonella in individuals under 19 years old was around 43.7% (12). Thus, the following method was used to estimate the minimum sample size required for this study: n = 4p × (1 − p)/d² = 600, where p =0.4, and d =0.1p. This study was conducted in accordance with the Helsinki Declaration (as revised in 2013). This study was approved by ethics board of Xiangnan University (No. XNXY2017031), and informed consent was obtained from all the patients’ parents.

Isolation and identification of Salmonella

Expansion

Stool swabs containing Cary-Blair transport culture medium were inoculated into selenite bright green (SBG) sulfonamide enrichment broth and cultured at 36 °C for 18 to 24 hours.

Isolation

An inoculating loop was used to inoculate the broth into Salmonella colorimetric culture medium, which was cultured at 36 °C for 18 to 24 hours.

Purification

Purple or wine-colored colonies on the Salmonella colorimetric culture medium were selected and transferred to a nutrient agar plate and cultured at 36 °C for 18 to 24 hours.

Biochemical identification

Single suspected colonies on the nutrient agar plate were selected and inoculated onto triple sugar iron (TSI) agar (K/A, gas production+, motile+, H2S+/− colonies), and the inoculum was then diluted with physiologic saline to a 0.5-McFarland standard of turbidity. A BioMérieux VITEK2 Compact biochemical analyzer (BioMérieux, Inc., Lyon, France) was subsequently used for identification.

Serotyping

Strains that were biochemically identified as Salmonella were adopted for serum coagulation tests, and the Kauffmann-White-LeMinor Serotyping Scheme was applied to determine the serotype.

Drug-sensitivity testing

The list of antibiotics for drug-resistance surveillance was determined based on the drug-sensitivity test and antibiotic selection principles recommended in Clinical and Laboratory Standards Institute (CLSI) documents M100-S27 and M45-A3. We applied the broth microdilution method for the drug-sensitivity testing of Salmonella strains and employed Escherichia coli ATCC25922 as the quality-control strain. The minimal inhibitory concentration was determined based on the CLSI standards, and the results were classified as resistant (R), intermediate (I), and sensitive (S). According to international expert proposal (18) and Chinese experts’ consensus on prevention and control of MDR organism healthcare-associated infection, 2015, strains that were resistant to ≥3 classes of antibiotics were defined as MDR strains.

A total of 10 classes and 14 antibiotics were tested: AMP, ampicillin/sulbactam (AMS), cefazolin (CFZ), cefoxitin (CFX), cefotaxime (CTX), ceftazidime (CAZ), imipenem (IPM), TET, NAL, CIP, chloramphenicol (CHL), gentamicin (GEN), trimethoprim/sulfamethoxazole (SXT), and AZI.

Statistical analysis

We used SPSS25.0 software (IBM Corp, New York, USA) for the statistical analysis of the data. The average age is presented as the median (P₂₅–P₇₅). The χ² test or Fisher’s exact-probability test was used for the rate comparisons. The significance level was set at α =0.05, and a P value <0.05 was considered statistically significant.

Results

Salmonella detection

A total of 1,263 pediatric samples were collected from 2017 through 2022 at two sentinel hospitals in Chenzhou, and Salmonella was detected in 221 cases (detection rate: 17.5%). The temporal distribution of Salmonella revealed that the detection rate fluctuated each year, with the highest detection rates (20% and above) observed in 2019 and 2020. Notably, the pathogen was principally detected in the 2^nd and 3^rd quarters of the years. In terms of the positive-detection rates, no statistically significant difference between the male and female pediatric patients was observed using the population distributions. The youngest patient with Salmonella diarrhea was 20 days old and the oldest was 15 years of age. The median age of the patients was 12 months (P₂₅–P₇₅: 9–18 months). At 21.3% and 17.8%, respectively, the Salmonella detection rates were the highest in pediatric diarrhea patients aged <12 months and 1–3 years (see Table 1).

Salmonella serotype distribution

Serotyping was on the 221 Salmonella strains, was done 32 serotypes identified, of which S. Typhimurium was dominant (79.2%), followed by S. Enteritidis (2.7%), Salmonella Litchfield (S. Litchfield) (1.8%), and S. Derby (1.4%). The other 28 serotypes were detected in 1–2 strains (see Table 2).

Drug-sensitivity test results

The 221 Salmonella strains were used for drug-sensitivity testing using 10 classes and 14 antibiotics, and drug resistance was high. The following six antibiotics had drug-resistance rates >40%: TET (86.9%), AMP (75.6%), AMS (58.4%), CFZ (55.7%), CHL (54.3%), and SXT (45.2%). The resistance rates for AMP, AMS, CFZ, CAZ, and CTX fluctuated over the years (P<0.05), but drug-resistance changes for the remaining antibiotics in years 2017–2022 inclusive did not differ (see Table 3).

Of the 221 Salmonella strains, 169 (76.5%) were MDR strains, the most common strain of which exhibited resistance to six (22.2%) and five (16.3%) drug classes, while 48.9% (108/221) of the strains were resistant to five or more classes (see Table 4). The drug-resistance spectrum for MDR is complex and the most common drug-resistance spectrum was observed for AMP-AMS-TET-CHL-CFZ-SXT, accounting for 10.9% (24/221), followed by AMP-TET-CHL-CFZ-SXT, AMP-CAZ-TET-CTX-CFZ, AMP-AMS-TET, and AMP-CAZ-AMS-TET-CTX-CFZ in seven, seven, six, and six strains, respectively. The other drug-resistance spectra were not present in more than five strains. Notably, five strains were resistant to ≥10 antibiotics, of which the most robust strain was resistant to nine drug classes and 13 antibiotics with a resistance spectrum of AMP-CAZ-AMS-TET-NAL-CFX-CHL-CTX-CFZ-GEN-SXT-AZM-CIP.

Discussion

The results of this investigation showed that the Salmonella detection rate in pediatric patients with foodborne infectious diarrhea in Chenzhou from 2017 through 2022 was 18.2%. The analysis of its temporal distribution revealed that there were some fluctuations in the annual detection rate. In both 2017 and 2018, the detection rate was approximately 10%, while after 2019, the detection rate was 15% or even 20%. Thus, the prevalence of salmonellosis in children showed an increase. Salmonellosis can occur anytime throughout the year, but it typically occurred from April to September, which is consistent with the findings of other related reports (19,20). This period comprises summer and autumn, and warm months with high environmental temperatures are conducive to the reproduction of Salmonella, and the overlap of summer and rainy season peaks which increases the risk of foodborne transmission of Salmonella (21).

The population-distribution results also revealed that there were no differences in salmonellosis between the children in terms of sex. Salmonellosis principally occurred in pediatric patients aged <3 years (i.e., 39.1% of the cohort), and was detected in only one neonate; and the overall detection rate in pediatric patients >4 years was significantly reduced. This might be due to the low degree of hand hygiene practices in infants and toddlers in this age group (22). In addition, the immature gut microbiota of the infants and toddlers might be a reason for the high infection rate of this population, some researchers have found that Clostridium sporogenes and facultative anaerobic bacteria in the mature gut microbiota inhibited the growth of Salmonella by maintaining epithelial hypoxia and competitive oxygen consumption (23). Due to the immature gut microbiota of infants and toddlers, their bodies’ ability to eliminate Salmonella that colonize the gut is likely reduced. In addition, severe acute gastroenteritis tends to occur after salmonellosis in high-risk populations, such as infants and toddlers, and other immunocompromised patients (24), resulting in higher-outpatient consultation and hospitalization rates relative to children in other age groups.

The circulating Salmonella serotypes differ worldwide and researchers have ascertained that the Salmonella serotypes isolated from children and adults are distinct (12); however, S. Typhimurium and S. Enteritidis nevertheless show a global prevalence (4) and have an extensive distribution in developing countries (24). In China, 70–80% of foodborne illness is caused by salmonellosis, and there are differences in Salmonella serotypes among different provinces, S. Typhimurium and S. Enteritidis are the classical and prevailing serotypes, particularly in those geographic regions in which S. Typhimurium constitutes the most common serotype (25-27). In the present study, the 221 Salmonella strains isolated from the pediatric diarrhea patients comprised 32 serotypes, of which S. Typhimurium accounted for 79.2% and was the absolute dominant Salmonella strain in Chenzhou, followed by S. Enteritidis (2.7%); these rates are generally consistent with those reported in the aforementioned studies. We also detected 30 other serotypes, including Salmonella Stanley (S. Stanley), Salmonella Goldcoast (S. Goldcoast), Salmonella Bovismorbificans (S. Bovismorbificans), Salmonella Albany (S. Albany), and Salmonella Paratyphi B (S. Paratyphi B), which shows the diverse distribution of Salmonella serotypes; we fully expect this to arouse attention.

Antibiotics are used to treat salmonellosis in children. The European Society for Pediatric Infectious Diseases recommends the use of antibacterial drugs for high-risk children to reduce the risk of bacteremia and extraintestinal infection (28). However, due to the extensive use of antibacterial drugs, Salmonella drug resistance is becoming progressively more serious, and the treatment has thus become increasingly difficult. Authors have discerned differences in drug-resistance rates in different geographic regions (29,30); however, this might be due to disparities in the types and doses of antibiotics used in the various regions. The results of this investigation showed that drug resistance was severe in the Salmonella strains isolated from pediatric diarrhea patients in Chenzhou from 2017 through 2022, of whom over 70% were resistant to TET and AMP, and more than 60% were resistant to six antibiotics. Third-generation cephalosporins are presently the drug of choice for treating Salmonella infection of the gut, and oral AZI is used as a substitute (28,31). The results of this investigation showed that the resistance rates for these drugs did not exceed 20%, and that the rate for AZM resistance was only 3.6%. We also ascertained that the drug-resistance rate for the 2^nd-generation cephalosporin CFX was only 2.3%, which is far lower than that for 3^rd-generation cephalosporins. We speculate that this might be due to the low usage frequency of these drugs in clinical practice. The drug-resistance rate for fluoroquinolone was only 20%; however, such drugs are not suitable for children, who may cause joint cartilage toxicity (32). In our study, the drug with the lowest drug-resistance rate was IPM, and only two strains were resistant (0.9%). However, this should also provoke scrutiny, as this antibiotic is strictly controlled in clinical practice, has a low rate of clinical usage, and is currently the last line of defense for treating MDR.

The MDR rate for foodborne salmonellosis in children in Chenzhou was 76.5%, and the most common drug-resistance spectrum was AMP-AMS-TET-CHL-CFZ-SXT. In addition, a considerable number of Salmonella strains were resistant to five or more antibiotics (48.9%), creating a dire situation. One group of authors demonstrated that the ratio of MDR strains was different among different Salmonella serotypes (33), and that the MDR rate for S. Typhimurium was significantly higher than the rate for other serotypes (34,35); S. Typhimurium was also the absolute dominant serotype in Chenzhou. However, a high population density, gross domestic product per capita, medical resources, and educational level may also affect the MDR level of foodborne pathogens (36). We expect to examine the relationships between these factors and MDR to provide a more solid foundation for clarifying the control of drug resistance in foodborne pathogens.

Conclusions

As the samples in the present study were primarily obtained from two sentinel hospitals as part of foodborne-illness surveillance in this city, they may not be completely representative of the patients in the region. In addition, the coronavirus disease 2019 pandemic might have reduced the willingness of some patients to attend hospitals, which might have affected the detection rates of Salmonella and created a bias in our results. Therefore, there is a definite need to expand the current sample size and conduct multicenter studies in the future.

In summary, this study found that foodborne salmonellosis in children in Chenzhou mainly occurred in the 2^nd and 3^rd quarters of the year, and had a high prevalence overall in infants and toddlers. S. Typhimurium accounted for the absolute majority of pathogenic Salmonella. Salmonella drug resistance appears to be currently widespread in Chenzhou, and the MDR problem is quite serious. This study had some limitations, but we posit that it will nevertheless facilitate the optimization of public health policy and thus provide a reference for preventing salmonellosis in children, guide rational antibiotic use in clinical practice, and arrest the continuous spread of Salmonella drug resistance.

Acknowledgments

Funding: This work was supported by the Science and Technology Innovation Ability Training Program of the Science and Technology Bureau’s of Chenzhou (No. ZDYF2020200), The Technology Research and Development Center of Chenzhou (ChenKeFa [2021] No. 57), the Scientific Research Fund of Hunan Province Health Commission (No. 202101062143), and the Innovation and Entrepreneurship Training Program for College Students of Hunan Province (No. S202310545023S).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-120/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-120/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-120/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-120/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Helsinki Declaration (as revised in 2013). This study was approved by ethics board of Xiangnan University (No. XNXY2017031), and informed consent was obtained from all the patients’ parents. The Chenzhou No. 1 and No. 4 People’s Hospital were informed and agreed with this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Rambach A. New plate medium for facilitated differentiation of Salmonella spp. from Proteus spp. and other enteric bacteria. Appl Environ Microbiol 1990;56:301-3. [Crossref] [PubMed]
2. D'Aoust JY. Pathogenicity of foodborne Salmonella. Int J Food Microbiol 1991;12:17-40. [Crossref] [PubMed]
3. Bula-Rudas FJ, Rathore MH, Maraqa NF. Salmonella Infections in Childhood. Adv Pediatr 2015;62:29-58. [Crossref] [PubMed]
4. Ferrari RG, Rosario DKA, Cunha-Neto A, et al. Worldwide Epidemiology of Salmonella Serovars in Animal-Based Foods: a Meta-analysis. Appl Environ Microbiol 2019;85:e00591-19. [Crossref] [PubMed]
5. Mughini-Gras L, Pijnacker R, Duijster J, et al. Changing epidemiology of invasive non-typhoid Salmonella infection: a nationwide population-based registry study. Clin Microbiol Infect 2020;26:941.e9-941.e14. [Crossref] [PubMed]
6. Popa GL, Papa MI. Salmonella spp. infection - a continuous threat worldwide. Germs 2021;11:88-96. [Crossref] [PubMed]
7. Hamilton KW, Cifu AS. Diagnosis and Management of Infectious Diarrhea. JAMA 2019;321:891-2. [Crossref] [PubMed]
8. Galanis E, Lo Fo Wong DM, Patrick ME, et al. Web-based surveillance and global Salmonella distribution, 2000-2002. Emerg Infect Dis 2006;12:381-8. [Crossref] [PubMed]
9. European Food Safety Authority. The European Union One Health 2019 Zoonoses Report. EFSA J 2021;19:e06406. [PubMed]
10. Tack DM, Ray L, Griffin PM, et al. Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016-2019. MMWR Morb Mortal Wkly Rep 2020;69:509-14. [Crossref] [PubMed]
11. Kim SH, Sung GH, Park EH, et al. Serotype Distribution and Antimicrobial Resistance of Salmonella Isolates in Korea between 2016 and 2017. Ann Lab Med 2022;42:268-73. [Crossref] [PubMed]
12. Judd MC, Hoekstra RM, Mahon BE, et al. Epidemiologic patterns of human Salmonella serotype diversity in the USA, 1996-2016. Epidemiol Infect 2019;147:e187. [Crossref] [PubMed]
13. Cellucci T, Seabrook JA, Chagla Y, et al. A 10-year retrospective review of Salmonella infections at the Children's Hospital in London, Ontario. Can J Infect Dis Med Microbiol 2010;21:78-82. [Crossref] [PubMed]
14. Plumb ID, Brown AC, Stokes EK, et al. Increased Multidrug-Resistant Salmonella enterica I Serotype 4,[5],12:i:- Infections Associated with Pork, United States, 2009-2018. Emerg Infect Dis 2023;29:314-22. [Crossref] [PubMed]
15. European Food Safety Authority. The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2018/2019. EFSA J 2021;19:e06490. [PubMed]
16. Zhan Z, Xu X, Gu Z, et al. Molecular epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonella in China, 2007-2016. Infect Drug Resist 2019;12:2885-97. [Crossref] [PubMed]
17. Chen K, Yang C, Chan EW, et al. Emergence of Conjugative IncC Type Plasmid Simultaneously Encoding Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin in Salmonella. Antimicrob Agents Chemother 2021;65:e0104621. [Crossref] [PubMed]
18. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268-81. [Crossref] [PubMed]
19. Powell MR, Crim SM, Hoekstra RM, et al. Temporal patterns in principal Salmonella serotypes in the USA; 1996-2014. Epidemiol Infect 2018;146:437-41. [Crossref] [PubMed]
20. Magossi G, Bai J, Cernicchiaro N, et al. Seasonal Presence of Salmonella spp., Salmonella Typhimurium and Its Monophasic Variant Serotype I 4,[5],12:i:-, in Selected United States Swine Feed Mills. Foodborne Pathog Dis 2019;16:276-81. [Crossref] [PubMed]
21. Aik J, Heywood AE, Newall AT, et al. Climate variability and salmonellosis in Singapore - A time series analysis. Sci Total Environ 2018;639:1261-7. [Crossref] [PubMed]
22. Haeusler GM, Curtis N. Non-typhoidal Salmonella in children: microbiology, epidemiology and treatment. Adv Exp Med Biol 2013;764:13-26. [Crossref] [PubMed]
23. Litvak Y, Mon KKZ, Nguyen H, et al. Commensal Enterobacteriaceae Protect against Salmonella Colonization through Oxygen Competition. Cell Host Microbe 2019;25:128-39.e5. [Crossref] [PubMed]
24. Gal-Mor O. Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae. Clin Microbiol Rev 2019;32:e00088-18. [Crossref] [PubMed]
25. Wei X, Long L, You L, et al. Serotype distribution, trend of multidrug resistance and prevalence of β-lactamase resistance genes in human Salmonella isolates from clinical specimens in Guizhou, China. PLoS One 2023;18:e0282254. [Crossref] [PubMed]
26. Zeng X, Lv S, Qu C, et al. Serotypes, antibiotic resistance, and molecular characterization of non-typhoidal salmonella isolated from diarrheic patients in Guangxi Zhuang Autonomous Region, China, 2014–2017. Food Control 2021;120:107478. [Crossref]
27. Shen H, Chen H, Ou Y, et al. Prevalence, serotypes, and antimicrobial resistance of Salmonella isolates from patients with diarrhea in Shenzhen, China. BMC Microbiol 2020;20:197. [Crossref] [PubMed]
28. Guarino A, Ashkenazi S, Gendrel D, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr 2014;59:132-52. [Crossref] [PubMed]
29. Medalla F, Gu W, Friedman CR, et al. Increased Incidence of Antimicrobial-Resistant Nontyphoidal Salmonella Infections, United States, 2004-2016. Emerg Infect Dis 2021;27:1662-72. [Crossref] [PubMed]
30. Faccone D, Lucero C, Albornoz E, et al. Emergence of azithromycin resistance mediated by the mph(A) gene in Salmonella Typhimurium clinical isolates in Latin America. J Glob Antimicrob Resist 2018;13:237-9. [Crossref] [PubMed]
31. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017;65:1963-73. [Crossref] [PubMed]
32. Patel K, Goldman JL. Safety Concerns Surrounding Quinolone Use in Children. J Clin Pharmacol 2016;56:1060-75. [Crossref] [PubMed]
33. Hur J, Jawale C, Lee JH. Antimicrobial resistance of Salmonella isolated from food animals: A review. Food Research International 2012;45:819-30. [Crossref]
34. Reis ROD, Souza MN, Cecconi MCP, et al. Increasing prevalence and dissemination of invasive nontyphoidal Salmonella serotype Typhimurium with multidrug resistance in hospitalized patients from southern Brazil. Braz J Infect Dis 2018;22:424-32. [Crossref] [PubMed]
35. Arguello H, Sørensen G, Carvajal A, et al. Prevalence, serotypes and resistance patterns of Salmonella in Danish pig production. Res Vet Sci 2013;95:334-42. [Crossref] [PubMed]
36. Collignon P, Beggs JJ, Walsh TR, et al. Anthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysis. Lancet Planet Health 2018;2:e398-405. [Crossref] [PubMed]

(English Language Editor: L. Huleatt)