Antibiotic stewardship: prescribing social norms
Authors: Ian M Gould, Timothy Lawes
Journal: The Lancet (2016)

With a burgeoning world population, expansions in medical intervention, and intensified agriculture, the need for antibiotic stewardship is increasingly clear.1Dar OA Hasan R Schlundt J et al.Exploring the evidence base for national and regional policy interventions to combat resistance.Lancet. 2016; 387: 285-295Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar Declining efficacy of antimicrobial prophylaxis for surgery or chemotherapy,2Teillant A Gandra S Barter D Morgan DJ Laxminarayan R Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.Lancet Infect Dis. 2015; 15: 1429-1437Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar and emergence of pan-resistant pathogens,1Dar OA Hasan R Schlundt J et al.Exploring the evidence base for national and regional policy interventions to combat resistance.Lancet. 2016; 387: 285-295Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar warn of a post-antibiotic era. In the evolutionary arms race of antimicrobial resistance, rejuvenating the neglected pipeline for new agents provides only a partial solution.3Outterson K Powers 3rd, JH Gould IM Kesselheim AS Questions about the 10 × '20 Initiative.Clin Infect Dis. 2010; 51: 751-752Crossref PubMed Scopus (3) Google Scholar The key challenge worldwide is translating awareness of resistance into effective stewardship.1Dar OA Hasan R Schlundt J et al.Exploring the evidence base for national and regional policy interventions to combat resistance.Lancet. 2016; 387: 285-295Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar In the past decade, the UK has made notable progress. A high media profile has provided political leverage to advance antimicrobial resistance up national health agendas, and surveillance systems for antibiotic consumption and resistance have been established.4Health Protection Scotland and Information Services DivisionReport on antimicrobial use and resistance in humans in 2012.https://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Publications/2014-01-28/2014-01-28-SAPG-2012-Report.pdfDate: 2014Google Scholar, 5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar National targets to reduce broad-spectrum antibiotic use have been associated with declines in Clostridium difficile and meticillin-resistant Staphylococcus aureus.5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar, 6Lawes T Lopez-Lozano JM Nebot CA et al.Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study.Lancet Infect Dis. 2015; 15: 1438-1449Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar However, declining sensitivities to substitute antibiotics4Health Protection Scotland and Information Services DivisionReport on antimicrobial use and resistance in humans in 2012.https://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Publications/2014-01-28/2014-01-28-SAPG-2012-Report.pdfDate: 2014Google Scholar suggest that without reducing total antibiotic consumption, we might be replacing rather than eliminating resistances.7Peterson LR Squeezing the antibiotic balloon: the impact of antimicrobial classes on emerging resistance.Clin Microbiol Infect. 2005; 11: 4-16Summary Full Text Full Text PDF PubMed Scopus (91) Google Scholar Sustaining progress will require a major shift in prescribing and consumption norms. A particular challenge in reducing antibiotic use is the disconnect between individual behaviour and population-level resistance. Avoiding overuse of a global common good requires making a diffuse and unrecognised social cost visible and felt. There is increasing interest in applying behavioural science, particularly in primary-care prescribing. In the UK, 80–90% of human antibiotic use occurs in the community, and large variation in prescribing rates are seen.5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar In a recent UK survey of over 1000 general practitioners (GPs), 28% reported prescribing antibiotics several times a week when uncertain of their necessity.8Cole A GPs feel pressurised to prescribe unnecessary antibiotics, survey finds.BMJ. 2014; 349: 5238Crossref Scopus (44) Google Scholar In The Lancet, Michael Hallsworth and colleagues9Hallsworth M Chadborn T Sallis A et al.Provision of social norm feedback to high prescribers of antibiotics in general practice: a pragmatic national randomised controlled trial.Lancet. 2016; (published online Feb 18.)http://dx.doi.org/10.1016/S0140-6736(16)00215-4PubMed Google Scholar provide evidence that social norm feedback to prescribers can be an effective method to reduce total antibiotic consumption in ambulatory care. Their national pragmatic randomised controlled trial (RCT) assessed two interventions targeting 1581 GP practices in England with the highest antibiotic prescribing rates in their areas. In the first intervention, GP practices in the intervention group received letters from England's Chief Medical Officer, which highlighted that their practice had prescribing rates higher than 80% of neighbouring practices, and resources for supporting self-care and delayed antibiotic prescriptions. In the second intervention, original control and intervention groups were re-randomised to a patient education campaign (posters and leaflets sent to practice managers) or a control group. During the first intervention, the rate of antibiotic items dispensed per 1000 weighted population—the primary outcome measure—was 126·98 (95% CI 125·68–128·27) in the intervention group and 131·25 (130·33–132·16) in the control group (incidence rate ratio [IRR] 0·967, 95% CI 0·957–0·977; p<0·0001). Over 6 months, this between group difference of 4·27 (3·3%) equated to 73 406 fewer antibiotic prescriptions. The patient-oriented intervention did not yield a significant additional benefit (antibiotic items dispensed per 1000 population: 135·00 [95% CI 133·77–136·22] in the patient-focused intervention group vs 133·98 [133·06–134·90] in the control group; IRR 1·01, 95% CI 1·00 to 1·02; p=0·105). Ethical and logistical considerations mean that most antibiotic stewardship interventions are assessed by observational or quasi-experimental studies.10Davey P Brown E Charani E et al.Interventions to improve antibiotic prescribing practices for hospital inpatients.Cochrane Database Syst Rev. 2013; 4 (CD003543)PubMed Google Scholar The efficient experimental design of this study strengthens confidence in causality. Reassuringly, the effect size was congruent with previous investigations on antibiotic prescriber feedback, although contamination through changes in antibiotic prescribing in controls could have led to an underestimate. Controls for patient characteristics and historic antibiotic use minimised common sources of confounding in cluster RCTs. The investigators did not assess the effects of the interventions on microbiological (resistance) outcomes, and did not record data for appropriateness of antibiotic use or harms from underuse. However, previous national and international studies have linked large variation in primary-care antibiotic use to resistance.4Health Protection Scotland and Information Services DivisionReport on antimicrobial use and resistance in humans in 2012.https://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Publications/2014-01-28/2014-01-28-SAPG-2012-Report.pdfDate: 2014Google Scholar, 5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar, 11Goossens H Ferech M Vander Stichele R Elseviers M ESAC Project GroupOutpatient antibiotic use in Europe and association with resistance: a cross-national database study.Lancet. 2005; 365: 579-587Summary Full Text Full Text PDF PubMed Scopus (1542) Google Scholar Furthermore, the largest effects of the feedback intervention were during winter, and in macrolide and penicillin use: Sweden's Strama programme showed that the restriction of common antimicrobial drugs for upper respiratory tract infections did not lead to an increase in complications.12Mölstad S Erntell M Hanberger H et al.Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish Strama programme.Lancet Infect Dis. 2008; 8: 125-132Summary Full Text Full Text PDF PubMed Scopus (199) Google Scholar A more important limitation of Hallsworth and colleagues' study is the short timescale of the intervention. It is not clear whether reiteration would be equally effective and whether, given time, it would shift, or merely narrow, the national antibiotic prescribing distribution. The national scale, pragmatic trial design, and low cost of the intervention suggest that social norm feedback could be effective and cost-saving in other settings. However, we note strong caveats. First, in a universal health-care system, the transaction costs of obtaining, publicising, and comparing prescribing data are low. Surveillance systems in other countries are increasingly being established, but with multiple providers aligned to different sociodemographic or clinical populations, meaningful comparisons are likely to be difficult. Second, effectiveness depends upon the salience of social norms to practitioner and patient behaviour. The public and practitioners in the UK are a "prepared field" after two decades of battling health-care-associated infections and with high media interest in resistance.4Health Protection Scotland and Information Services DivisionReport on antimicrobial use and resistance in humans in 2012.https://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Publications/2014-01-28/2014-01-28-SAPG-2012-Report.pdfDate: 2014Google Scholar, 5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar The absence of effect reported for the patient-oriented intervention could reflect saturation in public awareness. The reputational cost of deviance from prescribing norms, and use of a high-profile messenger (the Chief Medical Officer) might not provide as much leverage elsewhere. Third, social norms are only helpful where they converge with policy aims. A key message from behavioural sciences is that social factors affecting antibiotic prescribing and consumption norms are complex and context dependent.1Dar OA Hasan R Schlundt J et al.Exploring the evidence base for national and regional policy interventions to combat resistance.Lancet. 2016; 387: 285-295Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 11Goossens H Ferech M Vander Stichele R Elseviers M ESAC Project GroupOutpatient antibiotic use in Europe and association with resistance: a cross-national database study.Lancet. 2005; 365: 579-587Summary Full Text Full Text PDF PubMed Scopus (1542) Google Scholar Where health insurance or out-of-pocket expenditures predominate, doctor reputation and income depend upon answering patients' expectations for antibiotics.2Teillant A Gandra S Barter D Morgan DJ Laxminarayan R Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.Lancet Infect Dis. 2015; 15: 1429-1437Summary Full Text Full Text PDF PubMed Scopus (195) Google Scholar If patients can "shop" for antibiotics over the counter, a "race to the bottom" can occur.1Dar OA Hasan R Schlundt J et al.Exploring the evidence base for national and regional policy interventions to combat resistance.Lancet. 2016; 387: 285-295Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar It is also important to see the effect size in perspective. The investigators highlight that their feedback intervention could reduce primary-care prescribing in England by 0·85%, against a 5-year aim of reducing prescribing in primary care by 4%.5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar Between 2000 and 2014, UK primary-care antibiotic use expanded by 46%, from 14·3 to 20·9 defined daily doses per 1000 inhabitant-days.13European Centre for Disease Prevention and ControlAntimicrobial consumption interactive database (ESAC-Net).http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/esac-net-database/Pages/database.aspx#sthash.DqEHfHOl.dpufGoogle Scholar During the same period, antibiotic use fell in several European countries, and UK consumption is now twice that of the Netherlands (figure).13European Centre for Disease Prevention and ControlAntimicrobial consumption interactive database (ESAC-Net).http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/esac-net-database/Pages/database.aspx#sthash.DqEHfHOl.dpufGoogle Scholar Inpatient consumption also continues to increase.4Health Protection Scotland and Information Services DivisionReport on antimicrobial use and resistance in humans in 2012.https://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Publications/2014-01-28/2014-01-28-SAPG-2012-Report.pdfDate: 2014Google Scholar, 5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar Minimising discordance between public or practitioner norms and policy could be expected to sharpen efficacy and sustainability of stewardship. The feedback intervention was notably cheaper than NHS England's potentially divisive financial incentives for areas that reduce total antibiotic use by 1%.5Department of Health and Department for EnvironmentFoodRural AffairsUK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018.https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018Date: 2013Google Scholar The ethical principle of least restrictive means suggests self-regulation is preferable to top-down mandates. However, where externalities are high and evidence compelling (eg, seat-belt legislation or smoking bans), government may need to act early to create new norms before they are widely accepted. Hallsworth and colleagues make a clear case for integrating behavioural approaches into antibiotic stewardship, but interventions will need tailoring to regional contexts. The urgent, worldwide, and ecological nature of antibiotic resistance suggests that behavioural interventions should complement, rather than replace, top-down strategies. IMG has received consultancy and lecture fees from Bayer, Cubist, MSD, AstraZeneca, Novartis, Pfizer, and Clinigen; consultancy fees from The Medicines Company, Basilea, and GenMark; and non-financial support for consultancy from BioMérieux and Cepheid. As President of the International Society of Chemotherapy, IMG frequently requests meeting support from a wide range of diagnostic and pharmaceutical companies, including many of those involved in the manufacture of diagnostics and antibiotics for meticillin-resistant Staphylococcus aureus. TL declares no competing interests. Provision of social norm feedback to high prescribers of antibiotics in general practice: a pragmatic national randomised controlled trialSocial norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes. Full-Text PDF Open AccessStrong stewardship to fight antimicrobial resistanceAntibiotics have undoubtedly revolutionised medicine. However, widespread use of antimicrobial drugs in medicine and agriculture has spurred the evolution of pan-resistant bacterial strains. With few new antibiotics in the development pipeline, the threat to public health of antimicrobial resistance is all too real. Strong stewardship policies are urgently needed to stem inappropriate prescribing and use of antibiotics. Full-Text PDF