Abstract
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 were followed for at least 14 months. Intervention effects were assessed using interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed using metaregression.
Findings: Adjusted estimates showed reductions in total antibiotic DDDs per acute/medical admission (-4.8% per year, 95% CI: -9.1%,-0.2%) following the intervention. Among 7,160,421 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 adjusted 30-day mortality. Site-specific mortality trends were unrelated to the site-specific magnitude of antibiotic reduction (Spearman’s ρ=0.011, p=0.949). Whilst 90-day mortality odds appeared to increase (+3.9%, 95% CI: +0.5%,+7.4%), this was attenuated excluding admissions after COVID-19 onset (+3.2%, 95% CI:-1.5%,+8.2%). There was no evidence of intervention 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.
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 were followed for at least 14 months. Intervention effects were assessed using interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed using metaregression.
Findings: Adjusted estimates showed reductions in total antibiotic DDDs per acute/medical admission (-4.8% per year, 95% CI: -9.1%,-0.2%) following the intervention. Among 7,160,421 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 adjusted 30-day mortality. Site-specific mortality trends were unrelated to the site-specific magnitude of antibiotic reduction (Spearman’s ρ=0.011, p=0.949). Whilst 90-day mortality odds appeared to increase (+3.9%, 95% CI: +0.5%,+7.4%), this was attenuated excluding admissions after COVID-19 onset (+3.2%, 95% CI:-1.5%,+8.2%). There was no evidence of intervention 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.
| Original language | English |
|---|---|
| Number of pages | 15 |
| Journal | Lancet Infectious Diseases |
| DOIs | |
| Publication status | Published - 4 Oct 2022 |
Structured keywords
- Physical and Mental Health
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This is the final published version of the article (version of record). It first appeared online via Elsevier at https://doi.org/10.1016/S1473-3099(22)00508-4. Please refer to any applicable terms of use of the publisher.