Antibiotic resistant E. coli in children in rural Tanzania: Characterizing spatial and temporal patterns and risk factors for resistance

Background: Diarrheal infections are a significant cause of morbidity and mortality in young children in low-income countries. Enteroaggregative, enteropathogenic, and enterotoxigenic E. coli contribute significantly to the burden of diarrheal infections. Antibiotic resistance is increasingly common among bacterial pathogens including pathogenic E. coli. We monitored resistance to seven antibiotics in pathogenic and nonpathogenic fecal E. coli collected from young children participating in the PRET+ Study in rural Tanzania.;Methods: Mass drug treatment with azithromycin (MDA) was administered in 4 villages and four geographically matched communities served as controls. Rectal swabs were collected during cross-sectional surveys performed at baseline, 1-, 3-, and 6-months after MDA. Diarrheal stool samples were collected during the first 4 months of the study. E. coli isolated from fecal specimens were screened for susceptibility to azithromycin by E-test and erythromycin, ampicillin, amoxicillin/clavulanic acid, chloramphenicol, ciprofloxacin, and trimethoprim/sulfamethoxazole by disk diffusion. Diarrheagenic E. coli strains were identified using a multiplex polymerase chain reaction assay. We used logistic regression, hierarchical cluster analysis and spatial analysis techniques to assess the impact of antibiotic exposure and characterize the longitudinal patterns of carriage of antibiotic-resistant and pathogenic E. coli strains.;Results: MDA exposure was highly associated with azithromycin resistance carriage at 1-, 3-, and 6-months post-MDA. Carriage of ampicillin and trimethoprim/sulfamethoxazole resistant isolates was highly prevalent and ciprofloxacin resistance was rare. Resistance to nearly all antibiotics tested and multi-drug resistance occurred more frequently in pathogenic isolates. We found significant spatial and temporal variability in antibiotic-resistant and pathogenic E. coli carriage, but did not find consistent, statistically significant evidence of spatial clustering of antibiotic resistant or pathogenic E. coli in this population.;Conclusions: Our study supports the hypothesis that MDA results in significantly increased macrolide resistance carriage. While MDA is effective for trachoma elimination, it is not without costs; thus it is essential to monitor resistance. The suggested linkage between resistance and virulence in E. coli suggests hygiene and sanitation interventions could play a dual role in controlling transmission of pathogenic and antibiotic resistant strains. Broader study of human, animal, water and environmental samples may fill gaps in our understanding of antibiotic-resistant and pathogenic E. coli transmission.