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Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis

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Summary

Background

There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community by optimising antibiotic use.

Methods

We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum β-lactamase (ESBL) isolated from urine samples.

Findings

The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012–13 and an intervention period of 2014–17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect −15·9%, 95% CI −23·9 to −8·0) and cephalosporins (−22·6%, −35·9 to −9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by −0·028 cases per 1000 inhabitants (95% CI −0·034 to −0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of −65·6% (−68·2 to −63·0) 4 years later.

Interpretation

Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care.

Funding

Instituto de Salud Carlos III, Spanish Government (PI14/01523).

Introduction

The inappropriate use of antibiotics is one of the main factors responsible for antibiotic resistance.1 On April 30, 2014, WHO declared antimicrobial resistance as a serious threat to global public health and appealed to all countries to optimise their use of antimicrobials.2 Antimicrobial stewardship programmes (ASPs) are one of the key elements needed to achieve this goal.3 These interventions have proved useful in hospital settings,4, 5 but there is little evidence supporting the long-term sustainability and ecological impact of ASPs in primary care, where most antibiotics used in humans are prescribed6, 7 and up to a half of antibiotic prescriptions are inappropriate.8

Research in context

Evidence before this study

We searched the Cochrane Database of Systematic Reviews and PubMed for studies on antimicrobial stewardship in the community setting published before March 1, 2019, using the search terms “antimicrobial stewardship”, “antibiotic stewardship”, or “stewardship program”, in addition to the terms “primary care”, “community care”, “ambulatory care”, “antimicrobial resistance”, and “extended-spectrum-beta-lactamase-producing Escherichia coli”, with no date or language restrictions. We reviewed guidelines on antimicrobial stewardship programmes (ASPs) published by relevant international scientific societies. We retrieved additional publications from the authors' personal reference lists and the reference lists of included studies. We identified three systematic reviews pooling the evidence provided by these studies. In these studies, we found that the evidence on the efficacy of ASPs in primary care for improving antibiotic use was considered low to moderate. In addition, information about the association of key intervention components with improved prescribing and about the efficacy of educational interventions in changing clinicians' prescribing behaviour was scarce, as were data on the sustainability and large-scale applicability of ASPs in health-care systems at the community level. Most studies focused exclusively on respiratory tract infections, with little information about the effectiveness of ASPs in other infections. In particular, urinary tract infections, which are commonly misdiagnosed and overtreated, were underrepresented. There was also a paucity of studies designed to assess the ecological effect of ASPs in the community, with a very low level of evidence on substantial or persistent reductions in the incidence of resistant bacteria, including E coli producing extended-spectrum β-lactamase.

Added value of this study

Our study supports the efficacy of ASPs in primary care to improve antibiotic use and associated ecological effects, such as reducing urinary tract infections caused by E coli producing extended-spectrum β-lactamases. It reinforces the value of educational interventions in increasing adherence to reference guidelines and change the prescribing behaviour of clinicians, and, to our knowledge, includes for the first time regular one-to-one educational interviews as the core activity of an ASP. The programme and its findings are sustainable over time and enforceable in health-care systems at the community level.

Implications of all the available evidence

Our findings suggest that multimodal educational ASPs based on peer-to-peer educational interviews can be useful to improve the use of antimicrobials and reduce bacterial resistance in the community, and that these changes can be sustained over time. This information reinforces the recommendations to implement ASPs in primary care and should encourage further studies to confirm the usefulness of individual educational interviews.

In primary care, Escherichia coli is the most frequent cause of urinary tract infections (UTIs), which are one of the most common types of bacterial infections9 and are also the most frequently microbiologically diagnosed. Severe infections caused by Enterobacteriaceae producing extended-spectrum β-lactamase (ESBL) are associated with increased mortality rates.10 ESBL-producing bacteria frequently show co-resistance to other antibiotics such as fluoroquinolones.11

Antibiotic resistance in E coli is increasing throughout Europe, with the highest proportions of resistant isolates occurring in southern and south-eastern countries.12 Over the past 15 years, the prevalence of third-generation cephalosporin-resistant E coli, fluoroquinolone-resistant E coli, and ESBL-producing E coli has increased in Spain.13, 14 Antibiotic consumption in this country is higher than the European average and has significantly increased in between 2012 and 2016.15

In this worrying national context, we developed a primary-care ASP and did a quasi-experimental study to assess the effect of its implementation on antibiotic use and the incidence of ESBL-producing E coli isolated from urine samples in a population of nearly 2 million people in Andalusia, Spain. Our hypothesis was that the programme would result in sustained improved antibiotic prescribing and, consequently, would reduce the incidence of ESBL-producing E coli in primary care in the long-term.

Section snippets

Study design

This quasi-experimental, interrupted time-series study included doctors and all area residents from 214 primary health-care centres in four primary health-care districts in Spain (Aljarafe-Sevilla Norte, Huelva-Costa-Condado-Campiña, Sevilla, and Osuna), in coordination with microbiology laboratories at five reference hospitals (appendix p 1). The number of residents were recorded every quarter (appendix p 4). Patient data were anonymised, so informed consent was waived by the study's ethical

Results

The mean study population comprised 1 937 512 individuals (299 331 paediatric patients and 1 638 181 adult patients; appendix p 4) seen by 1387 prescribing physicians (1116 general practitioners and 271 paediatricians). There were 1 941 119 patients (304 814 children and 1 636 305 adults) in the area in the quarter before the start of the programme and 1 946 548 in the final quarter (289 555 children and 1 656 993 adults). The study was done from Jan 1, 2012, to Dec 31, 2017, spanning 24

Discussion

Our results show a positive long-term effect on antibiotic prescribing of an educational-based ASP, designed for the primary care setting, which had an excellent level of acceptance by clinicians. The ASP improved prescribing appropriateness and led to a reduction in the use of ciprofloxacin and cephalosporins, to an increase in the use of amoxicillin and fosfomycin trometamol, and to a decrease in the incidence of ESBL-producing E coli in the community across a health-care system.

Attention to

References (34)

  • J Rodríguez-Baño et al.

    Community infections caused by extended-spectrum β-lactamase–producing Escherichia coli

    Arch Intern Med

    (2008)
  • R Ben-Ami et al.

    A multinational survey of risk factors for infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in nonhospitalized patients

    Clin Infect Dis

    (2009)
  • J Rodríguez-Baño et al.

    Clinical significance of extended-spectrum β-lactamases

    Expert Rev Anti Infect Ther

    (2008)
  • Data from the ECDC Surveillance Atlas—antimicrobial resistance

  • R Canton et al.

    Antimicrobial susceptibility trends and evolution of isolates with extended spectrum beta-lactamases among Gram-negative organisms recovered during the SMART study in Spain (2011–2015)

    Rev Esp Quimioter

    (2018)
  • MA Díaz et al.

    Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido en hospitales españoles: segundo estudio multicéntrico (proyecto GEIH-BLEE 2006)

    Enferm Infecc Microbiol Clin

    (2009)
  • Antibiotic consumption in Europe

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