Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial - 26/01/23

Doi : 10.1016/S1473-3099(22)00508-4

Martin J Llewelyn, ProfPhD ^a,^{1
Joint first authors}⁎ , Eric P Budgell, MSc ^b,^{1
Joint first authors}, Magda Laskawiec-Szkonter, MA ^b,^c, Elizabeth L A Cross, BM BS ^a, Rebecca Alexander, MPharm ^e, Stuart Bond, PhD ^f, Phil Coles, MSc ^g, Geraldine Conlon-Bingham, MPharm ^h, Samantha Dymond, MPharm ⁱ, Morgan Evans, BMBS ^j, Rosemary Fok, MBBS ^k, Kevin J Frost, MSc ^l, Veronica Garcia-Arias, MSc ^m, Stephen Glass, MBBCh ⁿ, Cairine Gormley, MSc ^o, Katherine Gray, MBChB ^p, Clare Hamson, MBChB ^q, David Harvey, MBChB ^r, Tim Hills, BPharm ^s, Shabnam Iyer, FRCPath ^t, Alison Johnson, FRCPath ^u, Nicola Jones, PhD ^v, Parmjit Kang, MPharm ^w, Gloria Kiapi, MSc ^x, Damien Mack, FRCPath ^y, Charlotte Makanga, MSc ^z, Damian Mawer, MBChB ^aa, Bernie McCullagh, MSc ^ab, Mariyam Mirfenderesky, FRCPath ^ac, Ruth McEwen, MBChB ^ad, Sath Nag, FRCP ^ae, Aaron Nagar, MBBCh ^af, John Northfield, DPhil ^ag, Jean O’Driscoll, FRCPath ^ah, Amanda Pegden, MBBS ^ai, Robert Porter, MBBS ^aj, Neil Powell, MPharm ^ak, David Price, MD ^al, Elizabeth Sheridan, FRCPath ^am, Mandy Slatter, MSc ^an, Bruce Stewart, MBChB ^ao, Cassandra Watson, MPharm ^ap, Immo Weichert, MD ^aq, Katy Sivyer, DPhil ^ar, Sarah Wordsworth, ProfPhD ^d, Jack Quaddy, MSc ^b, Marta Santillo, PhD ^ar, Adele Krusche, DPhil ^ar, Laurence S J Roope, PhD ^d, Fiona Mowbray, PhD ^ar, Kieran S Hand, FRPharmS ^as, Melissa Dobson, BSc ^b,^c, Derrick W Crook, ProfFRCPath ^b,^v, Louella Vaughan, DPhil ^at, Susan Hopkins, FRCP ^y,^au, Lucy Yardley, ProfPhD ^ar,^av,^{†
Joint last authors}, Timothy E A Peto, ProfDPhil ^b,^v,^{†
Joint last authors}, Ann Sarah Walker, ProfPhD ^b,^{†
Joint last authors}

^a Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Falmer, UK

^b Nuffield Department of Medicine, University of Oxford, Oxford, UK

^c Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK

^d Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK

^e University Hospital of North Tees, Stockton-on-Tees, UK

^f Mid Yorkshire Hospitals NHS Trust, Wakefield, UK

^g Morriston Hospital, Swansea, UK

^h Craigavon Area Hospital, Portadown, UK

ⁱ Northern Devon Healthcare NHS Trust, Barnstaple, UK

^j Western General Hospital, Edinburgh, UK

^k University Hospitals Plymouth NHS Trust, Plymouth, UK

^l Airedale NHS Foundation Trust, Keighley, UK

^m Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK

ⁿ William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Ashford, UK

^o Pharmacy Department, Altnagelvin Area Hospital, Western Health and Social Care Trust, Londonderry, UK

^p Whiston Hospital, St Helens and Knowsley Teaching Hospitals NHS Trust, Prescot, UK

^q Cumberland Infirmary Carlisle, North Cumbria Integrated Care NHS Foundation Trust, Carlisle, UK

^r Wirral University Teaching Hospital NHS Foundation Trust, Upton, UK

^s Nottingham University Hospitals NHS Trust, Nottingham, UK

^t Royal Berkshire NHS Foundation Trust, Reading, UK

^u County Hospital, Wye Valley NHS Trust, Hereford, UK

^v John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK

^w The Royal Wolverhampton NHS Trust, Wolverhampton, UK

^x Great Western Hospitals NHS Foundation Trust, Swindon, UK

^y Royal Free London NHS Foundation Trust, London, UK

^z Betsi Cadwaladr University Health Board, Ysbyty Gwynedd, Bangor, UK

^aa York and Scarborough Teaching Hospitals NHS Foundation Trust, York, UK

^ab South Eastern Health and Social Care Trust, Ulster Hospital, Belfast, UK

^ac North Middlesex University Hospital NHS Trust, London, UK

^ad Countess of Chester Hospital NHS Foundation Trust, Chester, UK

^ae James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK

^af Antrim Area Hospital, Northern Health and Social Care Trust, Antrim, UK

^ag Milton Keynes Hospital NHS Foundation Trust, Milton Keynes, UK

^ah Buckinghamshire Healthcare NHS Trust, Stoke Mandeville, UK

^ai Chesterfield Royal Hospital NHS Foundation Trust, Chesterfield, UK

^aj Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

^ak Royal Cornwall Hospital NHS Trust, Truro, UK

^al Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK

^am Poole Hospital NHS Foundation Trust, Poole, UK

^an Royal United Hospitals Bath NHS Foundation Trust, Bath, UK

^ao East Surrey Hospital, Surrey and Sussex Healthcare NHS Trust, Redhill, UK

^ap London North West University Healthcare NHS Trust, Harrow, UK

^aq East Suffolk and North Essex NHS Foundation Trust, Ipswich, UK

^ar Centre for Clinical and Community Applications of Health Psychology, University of Southampton, Southampton, UK

^as Faculty of Health Sciences, University of Southampton, Southampton, UK

^at The Nuffield Trust, London, UK

^au UK Health Security Agency, London, UK

^av School of Psychological Science, University of Bristol, Bristol, UK

^* Correspondence to: Prof Martin J Llewelyn, Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Falmer, BN1 9PS, UK Department of Global Health and Infection Brighton and Sussex Medical School University of Sussex Falmer BN1 9PS UK

Summary

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.

Le texte complet de cet article est disponible en PDF.

Plan

Introduction

Methods

Study design

Clusters and participants

Randomisation and masking

Procedures

Outcomes

Statistical analysis

Role of the funding source

Results

Discussion

Data sharing

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Vol 23 - N° 2

P. 207-221 - février 2023 Retour au numéro

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Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial - 26/01/23

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