• Martin C Gulliford, Dorota Juszczyk, A Toby Prevost, Jamie Soames, Lisa McDermott, Kirin Sultana, Mark Wright, Robin Fox, Alastair D Hay, Paul Little, Michael Moore, Lucy Yardley, Mark Ashworth, and Judith Charlton.
• School of Population Health and Environmental Sciences, King's College London, London, UK.
• Health Technol Assess. 2019 Mar 1; 23 (11): 1-70.

BackgroundUnnecessary prescribing of antibiotics in primary care is contributing to the emergence of antimicrobial drug resistance.ObjectivesTo develop and evaluate a multicomponent intervention for antimicrobial stewardship in primary care, and to evaluate the safety of reducing antibiotic prescribing for self-limiting respiratory infections (RTIs).InterventionsA multicomponent intervention, developed as part of this study, including a webinar, monthly reports of general practice-specific data for antibiotic prescribing and decision support tools to inform appropriate antibiotic prescribing.DesignA parallel-group, cluster randomised controlled trial.SettingThe trial was conducted in 79 general practices in the UK Clinical Practice Research Datalink (CPRD).ParticipantsAll registered patients were included.Main Outcome MeasuresThe primary outcome was the rate of antibiotic prescriptions for self-limiting RTIs over the 12-month intervention period.Cohort StudyA separate population-based cohort study was conducted in 610 CPRD general practices that were not exposed to the trial interventions. Data were analysed to evaluate safety outcomes for registered patients with 45.5 million person-years of follow-up from 2005 to 2014.ResultsThere were 41 intervention trial arm practices (323,155 patient-years) and 38 control trial arm practices (259,520 patient-years). There were 98.7 antibiotic prescriptions for RTIs per 1000 patient-years in the intervention trial arm (31,907 antibiotic prescriptions) and 107.6 per 1000 patient-years in the control arm (27,923 antibiotic prescriptions) [adjusted antibiotic-prescribing rate ratio (RR) 0.88, 95% confidence interval (CI) 0.78 to 0.99; p = 0.040]. There was no evidence of effect in children aged < 15 years (RR 0.96, 95% CI 0.82 to 1.12) or adults aged ≥ 85 years (RR 0.97, 95% CI 0.79 to 1.18). Antibiotic prescribing was reduced in adults aged between 15 and 84 years (RR 0.84, 95% CI 0.75 to 0.95), that is, one antibiotic prescription was avoided for every 62 patients (95% CI 40 to 200 patients) aged 15-84 years per year. Analysis of trial data for 12 safety outcomes, including pneumonia and peritonsillar abscess, showed no evidence that these outcomes might be increased as a result of the intervention. The analysis of data from non-trial practices showed that if a general practice with an average list size of 7000 patients reduces the proportion of RTI consultations with antibiotics prescribed by 10%, then 1.1 (95% CI 0.6 to 1.5) more cases of pneumonia per year and 0.9 (95% CI 0.5 to 1.3) more cases of peritonsillar abscesses per decade may be observed. There was no evidence that mastoiditis, empyema, meningitis, intracranial abscess or Lemierre syndrome were more frequent at low-prescribing practices.LimitationsThe research was based on electronic health records that may not always provide complete data. The number of practices included in the trial was smaller than initially intended.ConclusionsThis study found evidence that, overall, general practice antibiotic prescribing for RTIs was reduced by this electronically delivered intervention. Antibiotic prescribing rates were reduced for adults aged 15-84 years, but not for children or the senior elderly.Future WorkStrategies for antimicrobial stewardship should employ stratified interventions that are tailored to specific age groups. Further research into the safety of reduced antibiotic prescribing is also needed.Trial RegistrationCurrent Controlled Trials ISRCTN95232781.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 11. See the NIHR Journals Library website for further project information.

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