Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England

Budgell, Eric; Davies, T.G.; Donker, Tjibbe; Hopkins, Susan; Wyllie, David; Peto, Tim; Gill, Martin J.; Llewelyn, Martin; Walker, A Sarah

doi:10.1016/j.jinf.2021.12.029

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…4 Although antibiotic use varies widely between and within health-care systems, no evidence exists that clinical outcomes are influenced by this wide variation (eg, between acute hospitals in England). 5 Antimicrobial stewardship aims to minimise resistance selection by ensuring that antibiotics are prescribed only when clinically indicated and that narrow-spectrum agents are used whenever appropriate. 6 However, translating research on antimicrobial stewardship into practice is hampered by the poor quality of evidence, particularly weaknesses in the intervention design process and the study designs used, which are usually underpowered, not experimental, and do not consider clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

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

Llewelyn

Budgell²,

Laskawiec-Szkonter³

et al. 2023

The Lancet Infectious Diseases

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Section: Introductionmentioning

confidence: 99%

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

Llewelyn

Budgell²,

Laskawiec-Szkonter³

et al. 2023

The Lancet Infectious Diseases

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“…The term "antimicrobial stewardship" is used to describe organisational level strategies to optimise antimicrobial use and minimise selection for AMR, and studies which evaluate different stewardship strategies typically compare organisations rather than individual patients [5]. Even within national healthcare systems, such as the National Health Service (NHS) in England, antimicrobial use varies widely between hospitals, both in terms of Defined Daily Doses (DDDs) of antibiotics prescribed per patient and the relative use of broad-spectrum vs narrow-spectrum agents [6].…”

Section: Introductionmentioning

confidence: 99%

Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing

Yokoyama

Peto²,

Budgell³

et al. 2023

PLoS ONE

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Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person’s faecal flora (their gut “resistome”). Using this approach, we aimed to test the hypothesis that differences in antimicrobial use across different hospitals in the United Kingdom will result in observable differences in the resistome of individual patients. Three National Health Service acute Hospital Trusts with markedly different antibiotic use and Clostridioides difficile infection rates collected faecal samples from anonymous patients which were discarded after C. difficile testing over a period of 9 to 15 months. Metagenomic DNA was extracted from these samples and sequenced using an Illumina NovaSeq 6000 platform. The resulting sequencing reads were analysed for taxonomic composition and for the presence of AMR genes. Among 683 faecal metagenomes we found huge variation between individuals in terms of taxonomic diversity (Shannon Index range 0.10–3.99) and carriage of AMR genes (Median 1.50 genes/cell/sample overall). We found no statistically significant differences in diversity (median Shannon index 2.16 (IQR 1.71–2.56), 2.15 (IQR 1.62–2.50) and 2.26 (IQR 1.55–2.51)) or carriage of AMR genes (median 1.37 genes/cell/sample (IQR 0.70–3.24), 1.70 (IQR 0.70–4.52) and 1.43 (IQR 0.55–3.71)) at the three trusts respectively. This was also the case across the sample collection period within the trusts. While we have not demonstrated differences over place or time using metagenomic sequencing of faecal discards, other sampling frameworks may be more suitable to determine whether organisational level differences in antibiotic use are associated with individual-level differences in burden of AMR carriage.

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“…5 Despite this, there is no evidence that clinical outcomes are influenced by the wide organisationallevel differences in antibiotic use that exist between acute hospitals in England. 6 Antimicrobial stewardship (AMS) aims to minimise resistance selection by ensuring antibiotics are only prescribed when clinically indicated and that narrow-spectrum agents are used whenever appropriate. 7 In primary care settings, AMS strategies that avoid or delay antibiotics are demonstrably safe and effective in controlling antibiotic overuse.…”

Section: Introductionmentioning

confidence: 99%

“…5 Despite this, there is no evidence that clinical outcomes are influenced by the wide organisational-level differences in antibiotic use that exist between acute hospitals in England. 6…”

Section: Introductionmentioning

confidence: 99%

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

Llewelyn

Budgell

Laskawiec-Szkonter

et al. 2022

Preprint

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BackgroundStrategies to reduce antibiotic overuse in hospitals depend on clinicians taking decisions to stop unnecessary antibiotics. There is a lack of evidence on how support clinicians do this effectively. We evaluated a multifaceted behaviour change intervention (ARK) which aims to reduce antibiotic consumption in hospitals by increasing decisions to stop antibiotics at clinical review.MethodsWe 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-daily-doses (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 non-elective 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.FindingsAdjusted 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/medical admissions, 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.InterpretationThe 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.FundingNIHR Programme Grants for Applied Research, RP-PG-0514-20015.Research in contextEvidence before this studyAcutely ill patients often need to receive antibiotics before full diagnostic information is available. Consequently, reducing overuse of antibiotics in hospitals requires clinicians to review and where appropriate, stop unnecessary antibiotic prescriptions. Evidence-based tools to support clinicians stop unnecessary antibiotics do not exist.We searched PubMed, with no language or date restrictions, on 31/January/2022 for clinical studies focused on improving antibiotic use for hospitalised adults using the terms “anti-bacterial agents therapeutic use” AND “antibiotic stewardship”. Among the 427 studies found, the great majority were uncontrolled evaluations of different approaches to education, decision support and feedback. These included one before-after study, which found no impact of unsupported clinician-led prescription review. Three small, hospital-level cluster-randomised trials were identified. One evaluated different approaches to feedback, one compared different hospital specialties and one found intense feedback to be effective. All were small and none considered clinical outcomes or sustainability. There is a need for research to deliver proven interventions ready for implementation into practice.Added value of this studyWe evaluated a multifaceted “Antibiotic Review Kit” (ARK) intervention to support prescribers to appropriately stop antibiotics at clinical review. ARK comprises a prescription decision-aid supported by a brief online training tool, guidance on implementation (including regular data collection and feedback) and a patient information leaflet. We found that the intervention was associated with a sustained reduction in hospital-level antibiotic use overall and of oral and narrow-spectrum antibiotics specifically. Weak trends were observed for 30-day mortality in opposite directions for immediate and sustained impact. Although there was a sustained increase in 90-day mortality after the intervention, this was only seen when analyses included patients admitted after the start of the COVID-19 pandemic. Taken together we conclude that these mortality effects are unrelated to the intervention.Implications of all available evidenceThe ARK intervention is safe and effective in reducing antibiotic use among adult medical hospital admissions. The tools used are now freely available for adoption into practice.

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Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England

Cited by 8 publications

References 47 publications

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

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

Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing

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

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