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PHE lead: Julie Robotham

 

Oxford University co-lead: Chris Butler

 

We will use this information generated in the populations theme to work out how we can reduce healthcare-associated infections and antimicrobial resistance, in ways the NHS can afford and that target those at highest risk. We will explore whether we should use drugs, tests for infections and vaccinations differently; or change the ways healthcare professionals interact with patients, empowering patients to manage their health and antibiotic use better.

Our strategy is to use multidisciplinary approaches to determine how antibiotic prescribing in primary care cab be sustainably reduced to the minimum safe level  and how can national, hospital and patient-focused approaches be combined to improve management and outcomes of AMR and HAI. We hope this will improve the effectiveness and cost-effectiveness of antimicrobial management and provide information on how to control difficult to treat infections.

 

Strategy​

To exploit multi-disciplinary approaches to complex interventions to answer the following key questions:​

  • How can antibiotic prescribing in primary care be sustainably reduced to the minimum safe level?​
  • How can national, hospital and patient-focused approaches be integrated to improve management and outcomes for AMR&HAI?​

4 overarching projects ongoing and planned, encompassing a portfolio of research​

 

 

Interventions Theme Projects 

Project Title 08:

Combine qualitative and quantitative methods to improve approaches to reducing antibiotic use across primary care 

Project Leads: Sarah Tonkin-Crine (OU), Julie Robotham (PHE), Sarah Wordsworth (OU), Chris Butler (OU) Researchers: Alice Ledda (PHE), HPRU health psychologist (OU) and Koen Pouwels (OU

Project started: April 2020 

We will conduct a portfolio of qualitative and quantitative research project to enhance understanding of approaches to reduce antibiotic use, for example “stopping the antibiotic course when you feel better”, antibiotic choice, and delayed prescribing.

We will: 

  • Carry out qualitative work to explore patient/public and primary care clinicians’ views of the concept of “stopping antibiotics when you feel better”. This will include initial focus groups or workshops with stakeholders to identify proposed approaches to incorporating this concept in primary care delivery. The work will be informed by earlier qualitative work in the ARK study, focused on a hospital setting. Interviews with clinicians and patients will explore individuals’ views of the different approaches and identify those which are most acceptable and feasible for a primary care context. Results will enable us to develop recommendations about whether and how “stopping antibiotics when you feel better” can be discussed between primary care clinicians and patients and the barriers and facilitators to clinicians having these discussions. 
  • Extend work being undertaken within the STEP-UP programme to explore implementation of delayed prescribing in general practice in the context of changes to healthcare delivery as a consequence of the COVID pandemic. This will include qualitative work, and potentially survey work with primary care clinicians, to understand how use of delayed prescriptions has changed (or not) for consultations being carried out remotely. Results will enable us to present recommendations on how delayed prescribing can be discussed and delivered in primary care when patients consult remotely. 
  • Alongside the qualitative work, develop a mathematical model of within-host pathogen and commensal dynamics under variable antibiotic treatment schedules to explore the potential impact of “stopping antibiotics when you feel better” considering the trade-off between treatment of the current infection and development of further resistance. The model will be modular, such that the different effects considering the pathogen, immune system and commensals can be adapted to specific clinical scenarios and to make use of available data. 
  • Conduct research exploring antibiotic choice and associated implications. Clinicians face choices between different antibiotics for patients e.g. narrow spectrum versus broad spectrum. Such choices can directly impact the spread of AMR. Understanding the drivers for particular treatment decisions could help identify policy levers to promote appropriate decisions. For example, a stated preference study could be used to investigate which clinical parameters drive the perception that narrow spectrum antibiotics will fail to cover the causative pathogen. Further, revealed preferences (what people actually do) can be investigated by looking at predictors of actual infection-related prescribing using, e.g., IORD, PHE dispensing data or QResearch data. The stated preferences (what people say they are likely to do) data can be brought together with the revealed preference data, to enhance predictions of behavioural change from introducing interventions that influence drivers of antibiotic choice. This could help inform decision making around intervention design and implementation.  
  • Apply for funding for a multi-arm study of antibiotic use for uncomplicated urinary tract infection (UTI), comparing dose, duration and antibiotic class effects on clinical outcomes.  There are a number of antibiotics that can be used for empirical prescribing for UTI in the community, and the evidence supporting different class, dose, and duration combinations is unclear. This can be leading to sub-optimal antibiotic selection and use. The impact of these permeations on UTI recurrence and resistance is not known. This multi-arm, multistage study, if funded, will provide answers that will inform primary care clinicians’ antibiotic prescribing decisions at scale, and will allow better appraisal of benefits and short and longer term clinical and microbiological outcomes. 
  • Based on a successful feasibility trial of cranberry extract for treating symptoms of complicated UTI that has just been completed, to develop an application for an adequately powered trial of this potentially antibiotic-sparing intervention. 

Key milestones and timescales: 

May 2021 - Prototype mathematical model of within-host dynamics evaluating “Stopping when you feel better” 

September 2021 - Design ‘antibiotic choice’ stated preference study submission of “Stopping when you feel better” mathematical model for peer reviewed publication.  

Qualitative data collection on “stopping antibiotics when you feel better” completed. Access necessary data for ‘antibiotic choice’ revealed preference study 

Dec 2021 - Qualitative data collection with clinicians on using delayed prescribing in remote consultations completed. 

March 2022 - Submission of qualitative paper on clinician/ patient/public views on “stopping antibiotics when you feel better”. 

Recommendations for primary care interventions to promote reduced antibiotic use. 

 

Project Title 09:

Use mathematical models to improve management of the most urgent AMR&HAI threat, CPE 

Project leads: Julie Robotham (PHE), Nicole Stoesser (OU) Researchers:  Alice Ledda (PHE), Diane Pople (PHE).  

Project started: April 2020 

  • To address the lack of understanding of CPE transmission dynamics, and limited evidence on the effectiveness of potential control measures we plan to undertake a programme of work to increase the evidence base on CPE dynamics and control to help inform practice in this high priority area.  
  • We will develop data-driven, individual-based, mathematical models of CPE transmission dynamics within hospitals, considering nosocomial transmission between patients and the contribution of the environment (e.g. sink biofilms) as a transmission source. Transmission parameters (human and environmental) are being estimated using Bayesian analysis of detailed data of admission, patient CPE testing and sink-sampling from a prospective study within an English Acute Trust (work in collaboration with the TRACE study and the University of Nottingham) and data from a survey conducted by PHE Porton of sinks in a sample of hospital wards. These models will be used to improve understanding of within-hospital transmission and evaluate screening and control strategies.  
  • We will investigate theoretical and data-driven approaches to understand intra-host dynamics of plasmid-mediated AMR spread in Enterobacteriales. Despite evidence that plasmids are a common vector in the spread of AMR genes, there remain many unknowns on the mechanisms. This gap can lead to available models being too general to enable specific predictions on resistance spread. We will review available data and models of intra-host plasmid dynamics and further develop these models to address gaps identified, making use of plasmid-mediated AMR genomic datasets (PHE). The aim being to create a more general model of intra-human-host plasmid dynamics, able to make predictions for clinical settings. While CPEs will be the main focus, we will also consider other resistances.   

Key milestones and timescales: 

July 2020: - Within-hospital CPE transmission dynamic model developed 

December 2020: - Bayesian framework for estimation of environmental sources to CPE transmission developed 

February 2021 - Submission of CPE within-hospital transmission model for peer review 

June 2021 - Draft of review paper on plasmid dynamics 

September 2021- Initial analysis of genomic data to inform models of plasmid dynamics 

March 2022 - Model of within-host plasmid dynamics developed 

 

Project title 10:

Modelling healthcare-associated COVID-19 * New project* 

Project leads: Julie Robotham (PHE), David Eyre (OU), Ben Cooper (OUResearchers: HPRU vacant posts: modelling 

Start Date: April 2020

Healthcare associated SARS-CoV-2 is a key concern within the COVID-19 pandemic. The contribution of nosocomial transmission to the spread of COVID-19 in England is not yet known.   

  • We will develop mathematical models of SARS-CoV-2 transmission in hospitals, working with both detailed individual NHS Hospital Trust and national data, to: explore the role of patients and healthcare workers in transmission, the relationship between hospital and community populations to understand transmission dynamics, determine the impact of interventions on transmission to inform national policy on hospital based interventions and control options.  

Key milestones and timescales: 

March 2021 - Submission of peer reviewed publication of models quantifying contribution of healthcare workers and patients to within-hospital transmission 

June 2021 - Model-based evaluation of hospital interventions 

December 2021 - Mathematical models developed exploring interplay between community and hospital dynamics 

 

Project title 11:

Control of C. difficile infection 

Project Leads: PHE leads: Mark Wilcox, Julie Robotham, OU leads: David Eyre, Koen Pouwels, Researchers: bioinformatician (Leeds), health economist, statistician (OU), software engineer (OU) 

Start date: October 2021 and continuing into year three 

For C. difficile, a key HAI still affecting >10000 patients/year, test national, hospital and individual approaches to improving management and outcomes 

  • We will evaluate implementation and costs/cost-effectiveness of a new national surveillance system (from current HPRU), specifically, assess information gain from sequencing one month’s isolates from 20 sentinel hospitals plus targeted whole genome sequencing (WGS) in putative outbreaks  
  • Test whether knowledge of patient movements/WGS could improve hospital control of C. difficile via a “tabletop” exercise linking 10 years of ward movements with WGS from faecal toxin-positive/toxin-negative C. difficile in Oxfordshire 
  • Assess the impact of toxin-negative cases (potentially infectious diarrhoea) on transmission and disease through WGS, longitudinal EHR, and modelling, specifically 
  • Combine patient-level antimicrobial, proton pump inhibitor and immunosuppressant usage with toxin-positive/negative WGS (approx. 1:1, sequencing 700 isolates) to investigate colonisation resistance and specific predictors of progression to toxin-positive disease  
  • Combine anonymised information on C. difficile testing algorithms from ~40 hospitals in an NIHR-funded behaviour intervention trial with PHE data, mathematical models of C. difficile transmission incorporating WGS from toxin-negative/toxin-positive cases, and hospital-specific data on faecal sampling and mandatory C. difficile testing rates to estimate yield, benefits/drawbacks and cost-effectiveness of different testing strategies 

Key milestones and timescales: 

December 2021 -  Complete implementation of new national surveillance system 

 

 

 

Interventions Theme Publications

Prospective trial of different antimicrobial treatment durations for presumptive canine urinary tract infections

Allerton F, Pouwels K, Bazelle J, Caddy S, Cauvin A, De Risio, Swann J, Warland J, Kent A

https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-021-02974-y

 

Investigating the mechanism of impact and differential effect of the Quality Premium scheme on antibiotic prescribing in England: a longitudinal study

Anyanwu P, Pouwels K, Walker A, Moore M, Majeed A, Hayhoe B, Tonkin-Crine S, Borek A, Hopkins S, Mcleod M, Costelloe C

https://bjgpopen.org/content/4/3/bjgpopen20X101052

 

Social and contextual influences on antibiotic prescribing and antimicrobial stewardship: A qualitative study with clinical commissioning group and general practice professionals

Borek AJ, Anthierens S, Allison R, Mcnulty CAM, Anyanwu PE, Costelloe C, Walker A, Bulter C, Tonkin-Crine S, STEP-UP Study Team

https://www.mdpi.com/2079-6382/9/12/859

 

STEP-UP study team. Implementing interventions to reduce antibiotic use: a qualitative study in high-prescribing practices

Borek A, Campbell A, Dent E, Butler C, Holmes A, Moore M, Walker A, Mcleod M, Tonkin-Crine S, STEP-UP Study Team

https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-021-01371-6

 

Optimising antimicrobial stewardship interventions in English primary care: a behavioural analysis of qualitative and intervention studies

Borek A, Wanat M, Akins L, Sallis A, Ashiru-Oredope D, Beech E, Butler C, Chadborn T, Hopkins S, Jone L, McNulty C, Robert N, Shaw K, Taborn E, Tonkin-Crine S

https://bmjopen.bmj.com/content/10/12/e039284.long

 

How did a Quality Premium financial incentive influence antibiotic prescribing in primary care? Views of Clinical Commissioning Group and general practice professionals?

Borek A, Anthierens S, Allison R, McNulty C, Lecky D, Costelloe C, Holmes A, Butler C, Walker A, Tonkin-Crine S,

https://academic.oup.com/jac/article/75/9/2681/5861493

 

Development of an intervention to support the implementation of evidence-based strategies for optimising antibiotic prescribing in general practice

Borek A, Campbell A, Dent E, Moore M, Butler CC, Holmes A, Walker AS, Mcleod M, Tonkin-Crine S, Anyanwu PE, Borek AJ, Bright N, Buchanan J, Butler CC, Campbell A, Costelloe C, Hayhoe B, Holmes A, Hopkins S, Majeed A, Mcleod M, Moore M, Morrell L, Pouwels KB, Robotham JV, Roope LSJ, Tonkin-Crine S, Walker AS, Wordsworth S, Wright C, Yadav S, Zalevski A

https://implementationsciencecomms.biomedcentral.com/articles/10.1186/s43058-021-00209-7

 

Impact of the COVID-19 Pandemic on Community Antibiotic Prescribing and Stewardship: A Qualitative Interview Study with General Practitioners in England

Borek A, Maitland K, Mcleod M, Campbell A, Hayhoe B, Butler C, Morrell L, Roope L, Holmes S, Walker A, Tonkin-Crine S, STEP-UP Study Team

https://www.mdpi.com/2079-6382/10/12/1531

 

Preferences for Medical Consultations from Online Providers: Evidence from a Discrete Choice Experiment in the United Kingdom

Buchanan J, Roope L, Morrell L, Pouwels K, Robotham J, Abel L, Crook D, Peto T, Butler C, Walker A, Wordsworth S

https://link.springer.com/article/10.1007/s40258-021-00642-8

 

Following the science? Views from scientists on government advisory boards during the COVID-19 pandemic: a qualitative interview study in five European countries

Colman E, Wanat M, Goossens H, Tonkin-Crine S, Anthierens S

https://gh.bmj.com/content/6/9/e006928

 

Understanding how community antiretroviral delivery influences engagement in HIV  are: a qualitative assessment of the Centralised Chronic Medication Dispensing and Distribution programme in South Africa

Dorward J, Msimango L, Gibbs A, Shozi H, Tonkin-Crine S, Hayward G, Butler C, Ngobese H, Drain P, Garrett N

https://bmjopen.bmj.com/content/10/5/e035412#

 

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study

Dorward J,  Sookrajh Y, Ngobese H, Lessells R, Sayed F, Bulo E, Moodley P, Samsunder N, Lewis L, Tonkin-Crine S, Drain P, Hayward G, Butler C, Garrett N

https://bmjopen.bmj.com/content/11/2/e045373

 

Probabilistic transmission models incorporating sequencing data for healthcare-associated Clostridioides difficile outperform heuristic rules and identify strain-specific differences in transmission

Eyre D, Laager M, Walker AS, Cooper BS, Wilson DJ

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008417

 

Feasibility and Acceptability of Community Coronavirus Disease 2019 Testing Strategies (FACTS) in a University Setting

Hirst J, Logan M, Fanshaww TR, Mwandigha L, Wanat M, Vicary C, Perera R, Tonkin-Crine S, Lee JJ, Tracey I, Duff G, Tufano P, Besharov M, Tarassenko L, Nicholson BD, Hobbs FDR

https://academic.oup.com/ofid/article/8/12/ofab495/6380918

 

Perspectives on COVID-19 testing policies and practices: a qualitative study with scientific advisors and NHS health care workers in England

Martindale A, Pilbeam C, Mableson H, Tonkin-Crine S, Atkinson P, Borek A, Lant S, Gobat N, Solomon T, Sheard S

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-021-11285-8

 

Delayed antibiotic prescription by general practitioners in the UK: A stated-choice study

Morrell L, Buchanan J, Roope L, Pouwels K, Butler C, Hayhoe B, Moore M, Tonkin-Crine S, McLeod M, Robotham J, Walker S, STEP-UP team

https://www.mdpi.com/2079-6382/9/9/608

 

Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: A choice experiment

Morrell L, Buchanan J, Roope LSJ, Pouwels KB, Butler CC, Hayhoe B, Tonkin-Crine S, Mcleod M, Robotham JV, Holmes A, Walker AS, Wordsworth S

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003737

 

Improving the uptake and SusTainability of Effective interventions to promote Prudent antibiotic Use and Primary care (STEP-UP) Team, Estimating the Effect of Healthcare-Associated Infections on Excess Length of Hospital Stay Using Inverse Probability–Weighted Survival Curves

Pouwels K, Vansteelandt S, Batra R, Edgeworth J, Wordsworth S, Robotham J, Anyanwu P, Borek A, Bright N, Buchanan J, Butler C, Campbell A, Costelloe C, Hayhoe B, Holmes A, Hopkins S, Majeed A, McLeod M, Moore M, Morrell L, Pouwels K, Robotham J, Roope L, Tonkin-Crine S, Walker A, Wordsworth S, Zalevski A

https://academic.oup.com/cid/article/71/9/e415/5734540

 

Awareness of appropriate antibiotic use in primary care for influenza-like illness: evidence of improvement from UK population-based surveys

Pouwels KB, Roope LSJ, Buchanan J, Morrell L, Tonkin-Crine S, Peters M, Jones L, Castro-Sánchez E, Crook D, Peto T, Butler C, Robotham J, Walker A, Wordsworth S

https://www.mdpi.com/2079-6382/9/10/690

 

Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey

Roope L, Buchanan J, Morrell L, Pouwels K, Sivyer K, Mowbray F, Abel L, Cross E, Yardley L, Peto T, Walker A, Llewelyn M, Wordsworth S

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01660-4

 

Reducing expectations for antibiotics in primary care: a randomised experiment to test the response to fear-based messages about antimicrobial resistance

Roope L, Tonkin-Crine S, Herd N, Michie S, Pouwels K, Castro-Sanchez E, Sallis A, Hopkins S, Robotham J, Crook D, Peto T, Peters M, Butler C, Walker A, Wordsworth S

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01553-6

 

Prescriber Commitment Posters to Increase Prudent Antibiotic Prescribing in English General Practice: A Cluster Randomized Controlled Trial

Sallis A, Bondaronek P, Sanders J, Yu L, Harris V, Vlaev I,  Sanders M, Tonkin-Crine S, Chadborn T

https://www.mdpi.com/2079-6382/9/8/490

 

Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice and subsequently change antibiotic use

Santillo M, Wanat M, Davoudianfar M, Bongard E, Savic S, Savic L, Porter C, Fielding J, Butler C, Pavitt S, Sandoe J, Tonkin-Crine S

https://bmjopen.bmj.com/content/10/10/e035793

 

Experiences and needs of persons living with a household member infected with SARS-CoV-2: A mixed method study

Verberk J, Anthierens S, Tonkin-Crine S, Goossens H, Kinsman J, de Hoog M, Bielicki J, Bruijning-Verhagen P, Gobat N

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249391

 

Transformation of primary care during the COVID-19 pandemic: experiences of healthcare professionals in eight European countries

Wanat M, Hoste M, Gobat N, Anastasaki M, Böhmer F, Chlabicz S, Colliers A, Farrell K, Karkana M-N, Kinsman J, Lionis C, Marcinowicz L, Reinhardt K, Skoglund I,  Sundvall P-D, Vellinga Akke, Verheij T, Goossens H, Butler C, van der Velden A, Anthierens S, Tonkin-Crine S

https://bjgp.org/content/71/709/e634

 

Optimising Interventions for Catheter-Associated Urinary Tract Infections (CAUTI) in Primary, Secondary and Care Home Settings

Wanat M, Logan M, Hirst J, Vicary C, Lee J, Perera R, Tracey I, Duff G, Tufano P, Fanshawe T, Mwandigha L, Nicholson B, Tonkin-Crine S, Hobbs R

https://www.mdpi.com/2079-6382/9/7/419

 

Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: a qualitative study of university students and staff

Wanat M, Logan M, Hirst J, Vicary C, Lee J, Perera R, Tracey I, Duff G, Tufano P, Fanshawe T, Mwandigha L, Nicholson B, Tonkin-Crine S, Hobbs R

https://bmjopen.bmj.com/content/11/9/e053850

 

Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians

Wanat M, Anthierens S, Butler C, Savic L, Savic S, Pavitt S, Sandoe JAT, Tonkin-Crine S

https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-021-01465-1

 

Supporting Primary Care Professionals to Stay in Work During the COVID-19 Pandemic: Views on Personal Risk and Access to Testing During the First Wave of Pandemic in Europe

Wanat M, Hoste M, Gobat N, Anastaski M, Bohmer F, Chlaicz S, Colliers A, Farrell K, Karkana M, Kinsman J, Lionis C, Marcinowicz L, Reinhardt K, Skogulnd I, Sundvall P, Vellingna A, Goossens H, Butler C, Velden AVD, Anthierens S, Tonkin-Crine S

https://www.frontiersin.org/articles/10.3389/fmed.2021.726319/full