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

BACKGROUND: Recent UK antibiotic stewardship policies have resulted in significant changes in primary care dispensing, but whether this has impacted antimicrobial resistance is unknown. AIM: To evaluate associations between changes in primary care dispensing and antimicrobial resistance in community-acquired urinary Escherichia coli infections. METHODS: Multilevel logistic regression modelling investigating relationships between primary care practice level antibiotic dispensing for approximately 1.5 million patients in South West England and resistance in 152,704 community-acquired urinary E. coli between 2013 and 2016. Relationships presented for within and subsequent quarter drug-bug pairs, adjusted for patient age, deprivation, and rurality. RESULTS: In line with national trends, overall antibiotic dispensing per 1000 registered patients fell 11%. Amoxicillin fell 14%, cefalexin 20%, ciprofloxacin 24%, co-amoxiclav 49% and trimethoprim 8%. Nitrofurantoin increased 7%. Antibiotic reductions were associated with reduced within quarter same-antibiotic resistance to: amoxicillin, ciprofloxacin and trimethoprim. Subsequent quarter reduced resistance was observed for trimethoprim and amoxicillin. Antibiotic dispensing reductions were associated with increased within and subsequent quarter resistance to cefalexin and co-amoxiclav. Increased nitrofurantoin dispensing was associated with reduced within and subsequent quarter trimethoprim resistance without affecting nitrofurantoin resistance. CONCLUSIONS: This evaluation of a national primary care stewardship policy on antimicrobial resistance in the community suggests both hoped-for benefits and unexpected harms. Some increase in resistance to cefalexin and co-amoxiclav could result from residual confounding. Randomised controlled trials are urgently required to investigate causality.