Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial
Year: 2022
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general 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 eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.
Source: The Lancet Infectious Diseases
Authors: Martin J Llewelyn, Eric P Budgell, Magda Laskawiec-Szkonter, Elizabeth L A Cross, Rebecca Alexander, Stuart Bond, Phil Coles, Geraldine Conlon-Bingham, Samantha Dymond, Morgan Evans, Rosemary Fok, Kevin J Frost, Veronica Garcia-Arias, Stephen Glass, Cairine Gormley, Katherine Gray, Clare Hamson, David Harvey, Tim Hills, Shabnam Iyer, Alison Johnson, Nicola Jones, Parmjit Kang, Gloria Kiapi, Damien Mack, Charlotte Makanga, Damian Mawer, Bernie McCullagh, Mariyam Mirfenderesky, Ruth McEwen, Sath Nag, Aaron Nagar, John Northfield, Jean O'Driscoll, Amanda Pegden, Robert Porter, Neil Powell, David Price, Elizabeth Sheridan, Mandy Slatter, Bruce Stewart, Cassandra Watson, Immo Weichert, Katy Sivyer, Sarah Wordsworth, Jack Quaddy, Marta Santillo, Adele Krusche, Laurence S J Roope, Fiona Mowbray, Kieran S Hand, Melissa Dobson, Derrick W Crook, Louella Vaughan, Susan Hopkins, Lucy Yardley, Timothy E A Peto, Ann Sarah Walker
Institutions: Brighton and Sussex Medical School, University of Sussex, East Surrey Hospital, Surrey and Sussex Healthcare NHS Trust, University of Oxford, Royal Devon & Exeter NHS Foundation Trust, Royal Devon University Healthcare NHS Foundation Trust, University Hospital of North Tees, Mid Yorkshire Hospitals NHS Trust, Morriston Hospital, Craigavon Area Hospital, Northern Devon Healthcare NHS Trust, Western General Hospital, University Hospitals Plymouth NHS Trust, Airedale NHS Foundation Trust, Hampshire Hospitals NHS Foundation Trust, William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Altnagelvin Area Hospital, Western Health and Social Care Trust, Mersey and West Lancashire Teaching Hospitals NHS Trust, Whiston Hospital, Cumberland Infirmary, North Cumbria Integrated Care NHS Foundation Trust, Wirral University Teaching Hospital NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Royal Berkshire NHS Foundation Trust, County Hospital, Wye Valley NHS Trust, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, The Royal Wolverhampton NHS Trust, Great Western Hospital, Great Western Hospitals NHS Foundation Trust, Royal Free London NHS Foundation Trust, Betsi Cadwaladr University Health Board, York Teaching Hospital NHS Foundation Trust, South Eastern Health and Social Care Trust, North Middlesex University Hospital NHS Trust, North Middlesex Hospital, Countess of Chester Hospital NHS Foundation Trust, James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Northern Health and Social Care Trust, Antrim Area Hospital, Milton Keynes Hospital NHS Foundation Trust, Buckinghamshire Healthcare NHS Trust, Chesterfield Royal Hospital NHS Foundation Trust, Royal Cornwall Hospital Trust, Royal Cornwall Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Poole Hospital NHS Foundation Trust, Royal United Hospital Bath NHS Trust, London North West Healthcare NHS Trust, East Suffolk and North Essex NHS Foundation Trust, University of Southampton, Nuffield Trust, UK Health Security Agency, University of Bristol
Language: English
Subfield: Applied Microbiology and Biotechnology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $6,000
Funders: Royal Devon and Exeter NHS Foundation Trust, Middlesex University, Nottingham University Hospitals NHS Trust, Betsi Cadwaladr University Health Board, Royal Free London NHS Foundation Trust, University Hospitals Plymouth NHS Trust, National Institute for Health Research Health Protection Research Unit, National Institute for Health and Care Research, Department of Health and Social Care, Imperial College London, University of Oxford, University of Nottingham, Cardiff University, University of Bristol, Newcastle upon Tyne Hospitals NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust, Manchester Biomedical Research Centre, Trinity College, University of Oxford, Programme Grants for Applied Research, NIHR Oxford Biomedical Research Centre
OpenAlex ID: W4301366235