Increased carriage of macrolide-resistant fecal E. coli following mass distribution of azithromycin for trachoma control

Background: Mass drug treatment with azithromycin (MDA) is part of the WHO-endorsed 'SAFE' strategy for trachoma control in endemic communities. MDA has been associated with reduced trachoma prevalence and short-term reductions in other bacterial infections, but can also lead to increased circulation of macrolide-resistant bacteria. Methods: We prospectively monitored macrolide resistance in fecal E. coli collected from young children participating in the PRET{thorn} Study in rural Tanzania. MDA was administered in four villages with >10% trachoma prevalence. Four nearby communities with lower trachoma prevalence served as controls. Rectal swabs were collected during crosssectional surveys performed at baseline, 1, 3 and 6 months after MDA. Fecal E. coli isolates were screened for macrolide susceptibility using disc diffusion and minimum inhibitory concentration methods. Cross-sectional and longitudinal differences in resistance prevalence by MDA exposure were compared using t-tests and logistic regression. Results: There was no difference in the proportion of individuals carrying azithromycinresistant E. coli at baseline (0.21 vs 0.16, P>0.05). Azithromycin resistance carriage prevalence remained stable over follow-up in non-MDA villages but increased sharply in MDA villages (0.61 at 1 month, 0.42 at 3 months and 0.31 at 6 months). MDA exposure was highly associated with azithromycin resistance carriage at 1 month post-MDA (OR 15.27, P<0.001) and subsequent surveys. Younger age and recent diarrhoea were also associated with increased odds of resistance (P<0.01). Conclusions: MDA resulted in significantly increased prevalence of macrolide resistance in E. coli. Although MDA is effective for trachoma elimination, it has costs; it is essential to monitor antimicrobial resistance following MDA.