Modelling the impact of antibiotic use on antibiotic-resistant Escherichia coli using population-based data from a large hospital and its surrounding community

Objectives: To determine the temporal relationship between antibiotic use and incidence of antibiotic-resistant Escherichia coli in both the inpatient and outpatient setting of a large urban area. Methods: A retrospective observational time-series analysis was performed to evaluate the incidence of non-duplicate clinical isolates of E. coli resistant to ciprofloxacin, trimethoprim/sulfamethoxazole and cefepime from January 2000 through December 2007, combined with a transfer function model of aggregated data on antibiotic use in both settings obtained from the hospital's pharmacy and outpatient billing offices. Results: Ciprofloxacin resistance increased from 6.0% (2000) to 15.4% (2007; P < 0.0001) and cefepime resistance from 0.9% (2002) to 3.2% (2007; P = 0.01). Trimethoprim/sulfamethoxazole resistance remained stable (23.7%-25.8%). Total antibiotic use increased in both settings, while fluoroquinolone use increased significantly only among outpatients. A temporal effect between fluoroquinolone resistance in community E. coli isolates and outpatient use of ciprofloxacin (immediate effect and time lag 1 month) and moxifloxacin (time lag 4 months) was observed, explaining 51% of the variance over time. The incidence of cefepime resistance in E. coli was correlated with ciprofloxacin use in the inpatient (lag 1 month) and outpatient (lag 4 months) settings and with the use of ceftriaxone (lag 0 month), piperacillin/tazobactam (3 months) and cefepime (3 months) in the hospital (R-2 = 51%). Conclusions: These results support efforts to reduce prescribing of fluoroquinolones for control of resistant E. coli including extended-spectrum beta-lactamase producers and show the added value of time-series analysis to better understand the interaction between community and hospital antibiotic prescribing and its spill-over effect on antibiotic resistance.