Antibiotic Review Kit for Hospitals (ARK-Hospital): a stepped wedge cluster randomised controlled trial

Background: Strategies to reduce antibiotic overuse in hospitals depend on clinicians reviewing antibiotics which have been started empirically. There is a lack of evidence on how to do this effectively. We evaluated a multifaceted behaviour change intervention (ARK) aimed at reducing antibiotic consumption in hospitals by increasing prescriber decisions to stop antibiotics at clinical review. Methods: We performed a stepped-wedge, hospital-level, cluster -randomised controlled trial using computer-generated sequence randomisation of 39 acute hospitals to 7 calendar-time blocks (12/February/2018–01/July/2019). Co-primary outcomes were monthly antibiotic defined-dailydoses (DDD) per acute/medical admission (organisation-level, superiority) and all-cause 30-day mortality (patient-level, non-inferiority, margin 5%). Clusters were eligible if they admitted nonelective medical patients, could identify an intervention “champion” and provide pre-intervention data from February/2016. Sites were followed up for a minimum of 14 months. Intervention effects were assessed using interrupted time series analyses in each cluster. Overall effects were derived through random-effects meta-analysis, using meta-regression to assess heterogeneity in effects across prespecified factors. Trial registration was ISRCTN12674243. Findings: Adjusted estimates showed a year-on-year reduction in antibiotic consumption (-4.8%, 95%CI: -9.1%,-0.2%, p=0.042) following the ARK intervention. Among 7,160,421 acute/medicaladmissions, we observed a -2.7% (95%CI: -5.7%,+0.3%, p=0.079) immediate and +3.0% (95%CI: - 0.1%,+6.2%, p=0.060) sustained change in adjusted 30-day mortality. This mortality trend was not related to the magnitude of antibiotic reduction achieved (Spearman’s ρ=0.011, p=0.949). Whilst 90- day mortality odds appeared to increase over time (+3.9%, 95%CI:+0.5%,+7.4%, p=0.023), this was not observed among admissions before COVID-19 onset (+3.2%, 95%CI:-1.5%,+8.2%, p=0.182). Length of hospital stay was unaffected. Interpretation: The weak, inconsistent effects of the intervention on mortality are likely to be explained by the COVID-19 pandemic onset during the post-implementation phase. We conclude that the ARK-intervention resulted in sustained, safe reductions in hospital antibiotic use

Antibiotic Review Kit for Hospitals (ARK-Hospital): a stepped wedge cluster randomised controlled trial

Background: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotics. There is limited evidence on how to support this. We evaluated a multifaceted behaviour change intervention (ARK) designed to reduce antibiotic use among adult acute/medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. Methods: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of 39 hospitals in 7 calendar-time blocks in the United Kingdom (25/September/2017-01/July/2019). Randomised implementation date was concealed until 12 weeks before implementation, when local preparations were designed to start. Co-primary outcomes were monthly antibiotic defined-daily-doses (DDD) per adult acute/medical admission (hospital-level, superiority) and all-cause 30-day mortality (patient level, non-inferiority, margin 5%). Sites were eligible if they admitted non-elective medical patients, could identify an intervention “champion”, and provide study data. Sites werefollowed for at least 14 months. Intervention effects were assessed using interrupted timeseries analyses within each site, estimating overall effects through random-effects meta analysis, with heterogeneity across prespecified potential modifiers assessed using meta regression.Trial registration: ISRCTN12674243.Findings: Adjusted estimates showed reductions in total antibiotic DDDs per acute/medicaladmission (-4.8% per year, 95% CI: -9.1%,-0.2%) following the intervention. Among7,160,421 acute/medical admissions, there were trends towards -2.7% (95% CI: -5.7%,+0.3%) immediate and +3.0% (95% CI: -0.1%,+6.2%) sustained changes in adjusted30-day mortality. Site-specific mortality trends were unrelated to the site-specific magnitudeof antibiotic reduction (Spearman’s ρ=0.011, p=0.949). Whilst 90-day mortality oddsappeared to increase (+3.9%, 95% CI: +0.5%,+7.4%), this was attenuated excludingadmissions after COVID-19 onset (+3.2%, 95% CI:-1.5%,+8.2%). There was no evidence ofintervention effects on length-of-stay (p>0.4).Interpretation: The weak, inconsistent intervention effects on mortality are likely explained by the post-implementation onset of the COVID-19 pandemic. The ARK intervention resulted in sustained, safe reductions in antibiotic use among adult acute/medical inpatients. Funding: NIHR Programme Grants for Applied Research, RP-PG-0514-20015