Selection and co-selection of antibiotic resistances among Escherichia coli by antibiotic use in primary care: An ecological analysis.

BACKGROUND:The majority of studies that link antibiotic usage and resistance focus on simple associations between the resistance against a specific antibiotic and the use of that specific antibiotic. However, the relationship between antibiotic use and resistance is more complex. Here we evaluate selection and co-selection by assessing which antibiotics, including those mainly prescribed for respiratory tract infections, are associated with increased resistance to various antibiotics among Escherichia coli isolated from urinary samples. METHODS:Monthly primary care prescribing data were obtained from National Health Service (NHS) Digital. Positive E. coli records from urine samples in English primary care (n = 888,207) between April 2014 and January 2016 were obtained from the Second Generation Surveillance System. Elastic net regularization was used to evaluate associations between prescribing of different antibiotic groups and resistance against amoxicillin, cephalexin, ciprofloxacin, co-amoxiclav and nitrofurantoin at the clinical commissioning group (CCG) level. England is divided into 209 CCGs, with each NHS practice prolonging to one CCG. RESULTS:Amoxicillin prescribing (measured in DDD/ 1000 inhabitants / day) was positively associated with amoxicillin (RR 1.03, 95% CI 1.01-1.04) and ciprofloxacin (RR 1.09, 95% CI 1.04-1.17) resistance. In contrast, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR 0.92, 95% CI 0.84-0.97). CCGs with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR 1.34, 95% CI 1.10-1.59). CONCLUSION:Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications.