Electronically delivered interventions to reduce antibiotic prescribing for respiratory infections in primary care: cluster RCT using electronic health records and cohort study

## Abstract

**Background:** Unnecessary prescribing of antibiotics in primary care is contributing to the emergence of antimicrobial drug resistance.

**Objectives:** To 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).

**Interventions:** A 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.

**Design:** A parallel-group, cluster randomised controlled trial.

**Setting:** The trial was conducted in 79 general practices in the UK Clinical Practice Research Datalink (CPRD).

**Participants:** All registered patients were included.

**Main outcome measures:** The primary outcome was the rate of antibiotic prescriptions for self-limiting RTIs over the 12-month intervention period.

**Cohort study:** A 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 2007 to 2016.

**Results:** There 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 ≥ 95 years (RR 0.97, 95% CI 0.79 to 1.18). Antibiotic prescribing was reduced in adults aged between 15 and 94 years (RR 0.94, 95% CI 0.75 to 0.95), that is, one antibiotic prescription was avoided for every 72 patients (95% CI 40 to 200 patients) aged 15-94 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.

**Limitations:** The 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.

**Conclusions:** This 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 15-94 years, but not for children or the senior elderly.

**Future work:** Strategies 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 registration:** Current Controlled Trials ISRCTN95232781.

**Funding:** This 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.

**Keywords:** ANTIBIOTICS; BACTERIAL MENINGITIS; EMPYEMA; INTRACRANIAL ABSCESS; MASTOIDITIS; PERITONSILLAR ABSCESS; PNEUMONIA; PRIMARY CARE; RESPIRATORY TRACT INFECTIONS.

### Plain Language Summary

The overuse of antibiotics to treat infections is contributing to the rise of antibiotic resistance in bacteria. A trial was carried out to evaluate whether or not interventions delivered through general practice computer systems may be used to reduce antibiotic prescribing for self-limiting respiratory tract infections (RTIs). The study was carried out in 79 UK general practices. The study tested the effect of a webinar to introduce the trial interventions, which included monthly feedback reports of data for respiratory consultations and antibiotic prescriptions, as well as computer-delivered decision support tools. These interventions were specially developed for this study and were pre-tested with general practitioners and practice nurses. Over the 12-month intervention period, the antibiotic-prescribing rate was about 12% lower in the intervention trial arm than in the control arm. There was no effect of intervention in children aged < 15 years or adults aged ≥ 95 years, but antibiotic prescribing was reduced by about 16% in adults aged between 15 and 94 years. Assuming this was caused by the intervention, one antibiotic prescription was avoided per year for every 62 patients aged between 15 and 94 years and registered with a trial practice. The study found no evidence that the intervention might increase the risk of 12 bacterial infections. In addition, a follow-up study of 610 UK general practices not included in the trial was conducted. The study found 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 it may be possible to observe about one more case of pneumonia per year and one more case of peritonsillar abscess per decade, but no increase in other infections is likely. It can be concluded that electronically delivered interventions, including feedback of antibiotic-prescribing data for specific indications, may have the potential to reduce unnecessary antibiotic prescribing; however, antimicrobial stewardship interventions need to be tailored to particular age groups.

### Conflict of interest statement

Martin C Gulliford is a member of the Health Services and Delivery Research Board. A Toby Prevost is an employee of Imperial College London and is a member of the Public Health Research (PHR) Funding Board. Alastair D Hay is a member of the Health Technology Assessment (HTA) Clinical Trials Board. Paul Little is a member of the HTA Pandemic Influenza Board, the National Institute for Health Research Journals Library Board and the Programme Grants for Applied Research Expression of Interests – HTA Projects remit. Lucy Yardley is a member of the HTA Antimicrobial Resistance Themed Call Board, the HTA Efficient Study Designs Board and the PHR Funding Board. Michael Moore is a member of the government’s Advisory Committee on Antimicrobial Prescribing, Resistance and Healthcare Associated Infection.