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Antibiotic resistance is a global health crisis that requires urgent action to stop its spread. To counteract the spread of antibiotic resistance, we must improve our understanding of the origin and spread of resistant bacteria in both community and healthcare settings. Unfortunately, little attention is being given to contain the spread of antibiotic resistance in community settings (i.e., locations outside of a hospital inpatient, acute care setting, or a hospital clinic setting), despite some studies have consistently reported a high prevalence of antibiotic resistance in the community settings. This study aimed to investigate the prevalence of antibiotic resistance in commensal  Escherichia coli  isolates from healthy humans in community settings in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we synthesized studies conducted from 1989 to May 2020. A total of 9363 articles were obtained from the search and prevalence data were extracted from 33 articles and pooled together. This gave a pooled prevalence of antibiotic resistance (top ten antibiotics commonly prescribed in LMICs) in commensal  E. coli  isolates from human sources in community settings in LMICs of: ampicillin (72% of 13,531 isolates, 95% CI: 65–79), cefotaxime (27% of 6700 isolates, 95% CI: 12–44), chloramphenicol (45% of 7012 isolates, 95% CI: 35–53), ciprofloxacin (17% of 10,618 isolates, 95% CI: 11–25), co-trimoxazole (63% of 10,561 isolates, 95% CI: 52–73), nalidixic acid (30% of 9819 isolates, 95% CI: 21–40), oxytetracycline (78% of 1451 isolates, 95% CI: 65–88), streptomycin (58% of 3831 isolates, 95% CI: 44–72), tetracycline (67% of 11,847 isolates, 95% CI: 59–74), and trimethoprim (67% of 3265 isolates, 95% CI: 59–75). Here, we provided an appraisal of the evidence of the high prevalence of antibiotic resistance by commensal  E. coli  in community settings in LMICs. Our findings will have important ramifications for public health policy design to contain the spread of antibiotic resistance in community settings. Indeed, commensal  E. coli  is the main reservoir for spreading antibiotic resistance to other pathogenic enteric bacteria via mobile genetic elements.

High prevalence of antibiotic resistance in commensal Escherichia coli from healthy human sources in community settings