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

Abstract

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.

Antimicrobial resistance associations with national primary care antibiotic stewardship policy: Primary care-based, multilevel analytic study

“…Pouwels (2018 and 2019) reported co-selection of resistance to antibiotics associated with prescribing, but did not adjust for possible confounding factors. [19,31] No study has yet demonstrated the concerning rise in resistance we observed in relation to the decreased dispensing of some antibiotics. The explanation for this is not clear.…”

Quantifying the economic cost of antibiotic resistance and the impact of related interventions: rapid methodological review, conceptual framework and recommendations for future studies

“…In practice, antibiotic use can affect ABR against an antibiotic of a different class. For instance, amoxicillin, which is typically prescribed for respiratory tract infections, is associated with increased trimethoprim and ciprofloxacin resistance in Escherichia coli causing urinary tract infections [69,70]. Conversely, higher nitrofurantoin use was found to be associated with lower levels of trimethoprim and amoxicillin resistance, potentially due to collateral sensitivity or a negative correlation between resistance genes [69].…”

“…For instance, amoxicillin, which is typically prescribed for respiratory tract infections, is associated with increased trimethoprim and ciprofloxacin resistance in Escherichia coli causing urinary tract infections [69,70]. Conversely, higher nitrofurantoin use was found to be associated with lower levels of trimethoprim and amoxicillin resistance, potentially due to collateral sensitivity or a negative correlation between resistance genes [69]. Models relating (human) antibiotic consumption to ABR assume that the relationship is not confounded by between-country differences such as in infection prevention and control measures and agricultural antibiotics use.…”

Overuse of antibiotics: Can viral vaccinations help stem the tide?

“…Moreover, within England, the reported number of macrolide-resistant BSI for gram-positive bacteria increased between 2014 and 2018, even though prescribing for macrolides decreased in both hospitals and primary care [3]. Sustained or increased resistance in the absence of antibiotic exposure could be a result of multiple factors, including resistance genes imposing a negligible fitness cost, continued use of other antibiotics that are co-selecting for resistance, or lagged effects of antibiotic reductions [5].…”