Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study

Clin Microbiol Infect. 2018 Sep;24(9):972-979. doi: 10.1016/j.cmi.2017.12.026. Epub 2018 Jan 10.


Objectives: We quantified the impact of antibiotics prescribed in primary care for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin-resistant (CIP-RE) and extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), while accounting for household clustering.

Methods: Prospective cohort study from January 2011 to August 2013 at primary care sites in Belgium, Poland and Switzerland. We recruited outpatients requiring antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients), outpatients not requiring antibiotics (non-exposed patients), and one to three household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL-PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2 (S3).

Results: We included 300 households (205 exposed, 95 non-exposed) with 716 participants. Most exposed patients received nitrofurans (86; 42%) or fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples from 202 (28%) participants. Fluoroquinolone treatment caused transient suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE (aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of samples from 71 (10%) participants, with colonization not associated with antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95% CI 1.3-9.0), respectively.

Conclusions: These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae.

Keywords: Antimicrobial resistance; Collateral damage; Enterobacteriaceae; Extended-spectrum β-lactamase; Fluoroquinolone; Microbiota; Nitrofuran; Urinary tract infection.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Belgium
  • Child
  • Drug Resistance, Bacterial*
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Female
  • Fluoroquinolones / pharmacology
  • Fluoroquinolones / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Nitrofurans / pharmacology
  • Nitrofurans / therapeutic use
  • Outpatients
  • Poland
  • Prospective Studies
  • Switzerland
  • Treatment Outcome
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology
  • Young Adult


  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Nitrofurans