title: Effects of fluoroquinolone restriction (from 2007 to 2012) on resistance in Enterobacteriaceae: interrupted time-series analysis.
abstract: BACKGROUND
  Antibiotic stewardship is a key component in the effort to reduce healthcare-associated infections.
  
  
  OBJECTIVE
  To describe the implementation and analyse the impact of fluoroquinolone restriction on resistance in Enterobacteriaceae, focusing on urinary isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, which were historically almost universally resistant to fluoroquinolones.
  
  
  METHODS
  ESBL-producing E. coli hospital and community isolates, obtained between April 2009 and March 2012 from consecutive non-duplicate urine samples, were included in an interrupted time-series analysis based on a Poisson distribution model. Periods before and after fluoroquinolone restriction were compared. The trend in fluoroquinolone resistance in all urinary isolates of Enterobacteriaceae (N ≈ 20,000 per year) and blood culture isolates of E. coli (N ≈ 350) between 2009 and 2013 were also analysed.
  
  
  RESULTS
  A large decline in the percentage of ciprofloxacin-resistant ESBL-producing urinary E. coli isolates was observed in both hospital (risk ratio: 0.473; 95% confidence interval: 0.315-0.712) and community settings (0.098; 0.062-0.157). The decline was also marked in all urinary isolates of Enterobacteriaceae and E. coli isolates from blood cultures.
  
  
  CONCLUSIONS
  We conclude that reducing fluoroquinolone usage to a level of ≤2 defined daily doses per 100 occupied bed-days in hospital sufficiently removed selection pressure to allow resistant Enterobacteriaceae – specifically, the UK endemic strains of ESBL-producing E. coli – to revert back to fluoroquinolone susceptibility within a short span of four months. This was accompanied with a concomitant reduction in overall ESBL burden.
authors.affiliation: Department of Microbiology, Northumbria Healthcare NHS Foundation Trust, UK. Electronic address: jayanta.sarma@nhs.net.
authors.forename: J B
authors.initials: JB
authors.lastname: Sarma
authors.affiliation: Department of Microbiology, Northumbria Healthcare NHS Foundation Trust, UK.
authors.forename: B
authors.initials: B
authors.lastname: Marshall
authors.affiliation: Department of Microbiology, Northumbria Healthcare NHS Foundation Trust, UK.
authors.forename: V
authors.initials: V
authors.lastname: Cleeve
authors.affiliation: Department of Microbiology, Northumbria Healthcare NHS Foundation Trust, UK.
authors.forename: D
authors.initials: D
authors.lastname: Tate
authors.affiliation: Department of Microbiology, Northumbria Healthcare NHS Foundation Trust, UK.
authors.forename: T
authors.initials: T
authors.lastname: Oswald
authors.affiliation: Department of Pharmacy, Northumbria Healthcare NHS Foundation Trust, UK.
authors.forename: S
authors.initials: S
authors.lastname: Woolfrey
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D003428:Cross Infection / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000652:urine; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D065186:Interrupted Time Series Analysis / Q000379:methods; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases
keywords: Antimicrobial stewardship; Enterobacteriaceae; Fluoroquinolones; Interrupted time-series analysis