Exploring the relationship between primary care antibiotic prescribing for urinary tract infections, Escherichia coli bacteraemia incidence and antimicrobial resistance: an ecological study

https://doi.org/10.1016/j.ijantimicag.2018.08.013Get rights and content

Highlights

  • High antibiotic prescribing is associated with higher UTI-related E. coli BSI incidence at the practice level.

  • High trimethoprim prescribing is associated with higher trimethoprim-resistant E. coli BSI incidence at the practice level.

  • GP antibiotic stewardship could be important in reducing severe outcomes after UTI.

ABSTRACT

This study quantified the association between antibiotic prescribing for urinary tract infections (UTIs) and the incidence/antimicrobial susceptibility of UTI-related Escherichia coli bacteraemia in adult women in England. A national ecological study was conducted with data aggregated at GP practice level. The study population was adult female patients (>18 years) with reported UTI-related E. coli bacteraemia in England (2012–2014). Reports of bacteraemia from the national mandatory surveillance scheme were linked with E. coli blood culture susceptibility data (where available) and the correlation with primary care exposure to trimethoprim and nitrofurantoin was quantified using longitudinal multilevel models. The study included 19 874 patients from 5916 practices. The overall incidence of UTI-related E. coli bacteraemia in the study group did not change significantly (1.3% increase, 95% CI 0.1–2.7%; P = 0.074). However, after adjusting for practice characteristics, UTI-related E. coli bacteraemia incidence increased by 3.0% (P < 0.001) and 1.5% (P < 0.01) with each increasing quintile in trimethoprim and nitrofurantoin prescribing, respectively. The incidence of trimethoprim-resistant bacteraemia increased by 4.5% (P = 0.032) with each increasing quintile in trimethoprim prescribing and was not associated with nitrofurantoin prescribing. This study demonstrated an association between GP prescribing for UTIs and UTI-related E. coli bacteraemia incidence at the practice level and showed that higher prescribing of trimethoprim is associated with higher incidence of trimethoprim-resistant bacteraemia. Evidence is provided of the importance of prudent antibiotic prescribing in primary care to prevent the development of antibiotic resistance, placing patients at risk of subsequent severe infections.

Introduction

Antimicrobial resistance (AMR) is a growing problem in the UK and globally. Optimising the use of antibiotics is a high priority as one of the main drivers of AMR is their misuse [1], [2]. For this reason, antimicrobial stewardship programmes (ASPs) in secondary [3], [4] and primary [5], [6] care have been put in place in the UK and globally in recent years. One component of ASPs is the provision of evidence-based guidelines for antimicrobial prescribing. The link between antibiotic exposure and AMR (for urinary and respiratory tract infections) in primary care has been widely demonstrated in recent meta-analyses [7], [8], [9].

Failure to adequately treat urinary tract infections (UTIs) increases the likelihood that the causative bacteria (most commonly Escherichia coli) will invade the bloodstream, causing bacteraemia, which is a major cause of infectious disease morbidity and mortality [10], [11]. A recent study looking at 30-day all-cause mortality in E. coli bacteraemia patients found that while UTI-related bacteraemia had a lower associated case fatality rate (CFR) than bacteraemia with other underlying foci of infection, the high prevalence of UTIs at the population level meant that this cause was associated with the largest number of deaths [12]. Public Health England (PHE) reported that the incidence of E. coli bacteraemia in England increased by 15.6% (from 45.0 to 52.0 cases/100 000 population) between 2010 and 2014 [13] along with an increase in antibiotic prescribing since 2010 [14]. It was also found that areas with higher antibiotic prescribing frequently had higher rates of AMR [14]. In a review looking at the population-estimated bloodstream infection (BSI) burden in Europe, it was estimated that 1.2–1.4 million episodes of BSI occur per year, based on extrapolation of rates from studies in Denmark, Finland and the UK. The CFR was calculated to be between 13% and 20% and, while the estimated episodes and CFR were not specific to E. coli bacteraemia, E. coli is the most commonly reported aetiological agent of BSI [15]. Therefore, understanding the progression from a UTI to a BSI is important for reducing BSI-related morbidity and mortality and is now a major focus for the UK government.

This study aimed to explore whether a relationship exists at the practice level between antibiotic prescribing for UTIs and the occurrence of BSIs resulting from a UTI in the community setting in England. The study focused on a community resident patient cohort in which UTIs are most common (women aged >18 years). Most UTIs are managed in the primary care setting, hence the primary objectives were to assess the association between prescribing of the two main first-line antibiotics for UTI treatment (trimethoprim and nitrofurantoin) by general practitioners (GPs) and the incidence of (i) UTI-related E. coli bacteraemia in adult women by GP practice (Model 1) and (ii) trimethoprim-resistant UTI-related E. coli bacteraemia in adult women by GP practice (Model 2).

In addition, a secondary objective was to investigate the ratio of trimethoprim to nitrofurantoin prescribing by GP practice in order to examine the association between this ratio and the outcomes listed above.

Section snippets

Study population and data sources

The study population for this ecological study comprised adult (>18 years) female patients with E. coli bacteraemia notified to the national mandatory surveillance programme between January 2012 and December 2014 [16] with the source of the bacteraemia recorded as ‘urinary tract’. Antibiotic prescribing data for primary care providers compiled by the National Health Service (NHS) Business Services Authority [14], which had previously been collected in the annual English Surveillance Programme

Results

Between 1 January 2012 and 31 December 2014, 114 761 episodes of E. coli bacteraemia in adults were reported, 50 487 (44.0%) of which were in women. An underlying source of infection was recorded for 83% of bacteraemias in women. The main recorded primary sources were: urinary tract (53%); unknown source (21%); hepatobiliary (12%); gastrointestinal (excluding hepatobiliary) (5%); respiratory tract (3%) and other (3%). After de-duplication and exclusion of records without the urinary tract as

Principal findings

This study demonstrated an association, at the GP practice-level, between prescribing of the two currently recommended antibiotics for UTI treatment and the incidence of UTI-related E. coli bacteraemia in adult women. The increase in bacteraemia incidence associated with trimethoprim prescribing was higher than with nitrofurantoin prescribing. It was also demonstrated that higher prescribing of trimethoprim is associated with a higher incidence of UTI-related trimethoprim-resistant E. coli

Acknowledgments

The authors would like to thank Mehdi Minaji, Miroslava Mihalkova and Sabine Bou-Antoun for their assistance with data extraction from the PHE infection-related databases.

Funding

This work was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) [grant no. HPRU-2012-10047] in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London (London, UK) in partnership with Public Health England (PHE). The views expressed are those of

References (31)

  • R Laxminarayan et al.

    Antibiotic resistance—the need for global solutions

    Lancet Infect Dis

    (2013)
  • J Wilson et al.

    Trends among pathogens reported as causing bacteraemia in England, 2004–2008

    Clin Microbiol Infect

    (2011)
  • M Goto et al.

    Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe

    Clin Microbiol Infect

    (2013)
  • The evolving threat of antimicrobial resistance: options for action

    (2012)
  • D Ashiru-Oredope et al.

    Improving the quality of antibiotic prescribing in the NHS by developing a new antimicrobial stewardship programme: Start Smart—Then Focus

    J Antimicrob Chemother

    (2012)
  • TF Barlam et al.

    Executive summary: implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

    Clin Infect Dis

    (2016)
  • CAM. McNulty

    European Antibiotic Awareness Day 2012: general practitioners encouraged to TARGET antibiotics through guidance, education and tools

    J Antimicrob Chemother

    (2012)
  • JS Gerber et al.

    Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial

    JAMA

    (2013)
  • C Costelloe et al.

    Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis

    BMJ

    (2010)
  • BG Bell et al.

    A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

    BMC Infect Dis

    (2014)
  • A Bryce et al.

    Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis

    BMJ

    (2016)
  • KB Laupland et al.

    Population-based epidemiology and microbiology of community-onset bloodstream infections

    Clin Microbiol Rev

    (2014)
  • JK Abernethy et al.

    Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England

    Clin Microbiol Infect

    (2015)
  • PublicHealthEngland (PHE)

    English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) 2010 to 2014

    (2015)
  • English surveillance programme for antimicrobial utilisation and resistance (ESPAUR). Report 2014.

    (2014)
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