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Updated: Sep 2, 2025
Author Spotlight: Advancements in Understanding and Combatting Shigella Infections
Published on: February 9, 2024
Dissemination of Multiple Drug-Resistant Shigella flexneri 2a Isolates Among Pediatric Outpatients in Urumqi, China
Wenli Zhang1, Christine L Zhou2, Ying Hu3
1Department of Clinical Examination, The Children's Hospital, Urumqi, Xinjiang, China.
Abstract:
Multiple drug-resistant (MDR) Shigella isolates have been reported worldwide. Between May 2017 and September 2018, 55 Shigella flexneri 2a isolates were collected from 3322 stool samples of 0-10-year-old outpatients with diarrhea at the Children's Hospital of Urumqi, China. All isolates were characterized using serotyping, antimicrobial susceptibility testing, and whole-genome sequencing. A total of 54 of 55 (98.2%) isolates exhibited MDR phenotypes and had accumulated multiple resistance determinants, particularly of fluoroquinolones and cephalosporins preferred for shigellosis treatment: point mutations in quinolone resistance-determining regions (QRDRs) of topoisomerases (GyrA (S83L, D87N) and ParC (S80I) [n = 9]; GyrA (S83L) and ParC (S80I) [n = 45]) and acquisition of qnrS1 (n = 3) and blaCTX-M (n = 8). Over 70% of isolates acquired two point mutations of GyrA (S83L) and ParC (S80I) in QRDRs and 11 highly resistant isolates accumulated three point mutations in QRDRs or acquired qnrS1. Four S. flexneri 2a isolates from three single-nucleotide polymorphism clusters exhibited coresistance to ciprofloxacin, cefotaxime, or azithromycin (AZM), which are used as first- and second-line shigellosis treatment antimicrobials in clinics. Our data indicated that fluoroquinolones should be terminated in shigellosis treatment for outpatients in Urumqi. The transferable antimicrobial resistance determinants have been identified for third-generation cephalosporins and AZM. Novel strategies are urgently required for developing empirical medication to reduce the antimicrobial selective pressure and prevent dissemination of MDR S. flexneri 2a isolates.
Insights
Multiple drug-resistant Shigella flexneri 2a strains are prevalent in Urumqi, China, showing resistance to key antibiotics like fluoroquinolones and cephalosporins. This necessitates an urgent reevaluation of shigellosis treatment strategies.
Area of Science:
- Microbiology
- Genetics
- Public Health
Background:
- Multiple drug-resistant (MDR) Shigella isolates pose a global health threat.
- Shigellosis remains a significant cause of diarrheal disease, particularly in children.
- Emergence of resistance to preferred antimicrobial agents complicates treatment.
Purpose of the Study:
- To characterize the antimicrobial resistance profiles and genetic basis of MDR Shigella flexneri 2a isolates from pediatric outpatients in Urumqi, China.
- To assess the prevalence of specific resistance mechanisms, including point mutations and acquired resistance genes.
- To inform clinical treatment guidelines for shigellosis in the region.
Main Methods:
- Collection of Shigella flexneri 2a isolates from diarrheal stool samples of pediatric outpatients.
- Serotyping, antimicrobial susceptibility testing, and whole-genome sequencing of isolates.
- Analysis of point mutations in quinolone resistance-determining regions (QRDRs) and identification of acquired resistance genes.
Main Results:
- 98.2% of 55 Shigella flexneri 2a isolates exhibited MDR phenotypes.
- Common resistance mechanisms included point mutations in GyrA and ParC, and acquisition of qnrS1 and blaCTX-M genes.
- Four isolates showed co-resistance to ciprofloxacin, cefotaxime, or azithromycin, critical for shigellosis treatment.
- High rates of resistance to fluoroquinolones and cephalosporins were observed.
Conclusions:
- Fluoroquinolone use in shigellosis treatment for outpatients in Urumqi should be discontinued due to widespread resistance.
- Transferable resistance determinants for third-generation cephalosporins and azithromycin are present.
- Novel empirical treatment strategies are urgently needed to combat MDR Shigella flexneri 2a and reduce antimicrobial selective pressure.
