1 Dar OA

Hasan R

Schlundt J

et al. Exploring the evidence base for national and regional policy interventions to combat resistance. 2 Teillant 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. 1 Dar OA

Hasan R

Schlundt J

et al. Exploring the evidence base for national and regional policy interventions to combat resistance. 3 Outterson K

Powers 3rd, JH

Gould IM

Kesselheim AS Questions about the 10 × ‘20 Initiative. 1 Dar OA

Hasan R

Schlundt J

et al. Exploring the evidence base for national and regional policy interventions to combat resistance. With a burgeoning world population, expansions in medical intervention, and intensified agriculture, the need for antibiotic stewardship is increasingly clear.Declining efficacy of antimicrobial prophylaxis for surgery or chemotherapy,and emergence of pan-resistant pathogens,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.The key challenge worldwide is translating awareness of resistance into effective stewardship.

4 Health Protection Scotland and Information Services Division

Report on antimicrobial use and resistance in humans in 2012. , 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. , 6 Lawes 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. 4 Health Protection Scotland and Information Services Division

Report on antimicrobial use and resistance in humans in 2012. 7 Peterson LR Squeezing the antibiotic balloon: the impact of antimicrobial classes on emerging resistance. 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.National targets to reduce broad-spectrum antibiotic use have been associated with declines in Clostridium difficile and meticillin-resistant Staphylococcus aureus.However, declining sensitivities to substitute antibioticssuggest that without reducing total antibiotic consumption, we might be replacing rather than eliminating resistances.Sustaining progress will require a major shift in prescribing and consumption norms.

5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. 8 Cole A GPs feel pressurised to prescribe unnecessary antibiotics, survey finds. 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.In a recent UK survey of over 1000 general practitioners (GPs), 28% reported prescribing antibiotics several times a week when uncertain of their necessity.

9 Hallsworth 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. In The Lancet, Michael Hallsworth and colleaguesprovide 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).

10 Davey P

Brown E

Charani E

et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Ethical and logistical considerations mean that most antibiotic stewardship interventions are assessed by observational or quasi-experimental studies.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.

4 Health Protection Scotland and Information Services Division

Report on antimicrobial use and resistance in humans in 2012. , 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. , 11 Goossens H

Ferech M

Vander Stichele R

Elseviers M ESAC Project Group

Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. 12 Mölstad 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. 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.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.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.

4 Health Protection Scotland and Information Services Division

Report on antimicrobial use and resistance in humans in 2012. , 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. 1 Dar OA

Hasan R

Schlundt J

et al. Exploring the evidence base for national and regional policy interventions to combat resistance. , 11 Goossens H

Ferech M

Vander Stichele R

Elseviers M ESAC Project Group

Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. 2 Teillant 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. 1 Dar OA

Hasan R

Schlundt J

et al. Exploring the evidence base for national and regional policy interventions to combat resistance. 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.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.Where health insurance or out-of-pocket expenditures predominate, doctor reputation and income depend upon answering patients' expectations for antibiotics.If patients can “shop” for antibiotics over the counter, a “race to the bottom” can occur.

5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. 13 European Centre for Disease Prevention and Control

Antimicrobial consumption interactive database (ESAC-Net). 13 European Centre for Disease Prevention and Control

Antimicrobial consumption interactive database (ESAC-Net). 4 Health Protection Scotland and Information Services Division

Report on antimicrobial use and resistance in humans in 2012. , 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. 5 Department of Health and Department for Environment Food Rural Affairs

UK 5 year antimicrobial resistance (AMR) strategy 2013 to 2018. Figure Total consumption of antibiotics for systemic use* (A) and mean annual change in consumption of antibiotics in primary care (B) by European country, 2000–14 Show full caption 13 European Centre for Disease Prevention and Control

Antimicrobial consumption interactive database (ESAC-Net). Data from ESAC-Net (retrieved Dec 3, 2015).The UK is shown in red. *As defined in the WHO/ATX index (2012). DDDs=defined daily doses. 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%.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.During the same period, antibiotic use fell in several European countries, and UK consumption is now twice that of the Netherlands ( figure ).Inpatient consumption also continues to increase.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%.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.