What is the effect of trimethoprim/nitrofurantoin prescribing on the incidence and antibiotic susceptibility patterns of E. coli bacteraemia nationally at the GP practice level?

Problem

Bloodstream infections are a major cause of infectious disease morbidity and mortality both nationally and internationally. Between 2012 and 2015 the incidence of E. coli bloodstream infections in England increased by 10.4% from 60.4 to 66.23 per 100,000 population. The most commonly reported probable source of E. coli bacteraemia in England is urinary tract infection (UTI), with approximately 48% of E. coli bacteraemia suspected of originating from a UTI. This study aims to quantify the association between antibiotic prescribing for urinary tract infections (UTI) and the incidence and antibiotic susceptibility patterns of Escherichia coli bacteraemia originating from a UTI in England.

Approach

A national ecological study was conducted with all data being aggregated at the GP practice level. The study population was all female adult (18+) patients with a reported E. coli bacteraemia in England between January 1st, 2012 and December 31st, 2014 with the primary focus of the bacteraemia being recorded as a UTI. Primary care trimethoprim and nitrofurantoin prescribing data was obtained and antibiotic susceptibility data for E. coli isolates from blood and urine samples from Public Health England (PHE) surveillance systems were linked to PHE E. coli bacteraemia data. Longitudinal multi-level models were used to look at the correlation between GP prescribing levels of trimethoprim and nitrofurantoin and the incidence of E. coli bacteraemia (both susceptible and resistant) in adult women in England.

Findings

There were 19,874 adult female E. coli bacteraemia patients in the study from 5,916 GP practices. Over the study period, E. coli bacteraemia in women did not change significantly (1.3%, p=0.074), with the trend in trimethoprim prescribing decreasing by 83.7 DDD/1000 population year-on-year (p<0.001) and the trend in nitrofurantoin prescribing decreasing 3.9 DDD/1000 population year-on-year (p<0.01) over the study period. Of the 15,140 linked blood cultures, 7,888 (52.1%) were tested against trimethoprim with 46.6% being non-susceptible and 847 (5.6%) were tested against nitrofurantoin with 4.0% being non-susceptible. After adjusting for practice characteristics, E. coli bacteraemia increased by 2.5% (p<0.001) with each increasing quintile of trimethoprim prescribing and increased by 1.6% (p=0.001) with each increasing quintile of nitrofurantoin prescribing. Trimethoprim-resistant bacteraemia increased by 4.5% (p=0.032) with increased trimethoprim prescribing and decreased by 1.2% (p=0.546) with increased nitrofurantoin prescribing, the latter of which was not statistically significant.

Consequences

This study has demonstrated that there is an association between antibiotic prescribing for UTIs and the incidence of E. coli bacteraemia originating from a UTI. It has also demonstrated that higher prescribing of trimethoprim contributes to higher incidence of trimethoprim-resistant bacteraemia. This study provides further evidence of the importance of the adoption of and compliance with Antibiotic Stewardship Programs in primary care Trusts across England.