title: Increased carriage of macrolide-resistant fecal E. coli following mass distribution of azithromycin for trachoma control.
abstract: 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+ 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 cross-sectional 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 azithromycin-resistant 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.
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA jseidman@jhsph.edu.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Seidman
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Christian L
authors.initials: CL
authors.lastname: Coles
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Silbergeld
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Levens
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Harran
authors.initials: H
authors.lastname: Mkocha
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Lashaunda B
authors.initials: LB
authors.lastname: Johnson
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Muñoz
authors.affiliation: Department of International Health, Department of Environmental Health and Dana Center for Preventive Ophthalmology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Kongwa Trachoma Project, Kongwa, United Republic of Tanzania and Biology Department, Morgan State University, Baltimore, MD, USA.
authors.forename: Sheila K
authors.initials: SK
authors.lastname: West
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D024881:Drug Resistance, Bacterial; D019353:Endemic Diseases; D004926:Escherichia coli / Q000502:physiology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D018942:Macrolides; D008297:Male; D011446:Prospective Studies; D013636:Tanzania / Q000453:epidemiology; D014141:Trachoma / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017963:Azithromycin
keywords: Africa; Azithromycin; E. coli; antimicrobial resistance; children