Strategies to reduce the burden of antibiotic resistance in China

Lead Research Organisation: University of Bristol
Department Name: Social Medicine

Abstract

Antimicrobial resistance (AMR) and particularly resistance to antibiotics (ABR) has become one of the most complex public health challenges globally. Estimates have suggested that by 2050 AMR will be responsible for 10 million deaths, of which 4.73 million are in Asia, with an associated reduction of 2% to 3.5% in Gross Domestic Product (GDP) that will cost the world up to 100 trillion USD. Our collaborative research and training programme will bring together international experts at leading universities in China and the UK to tackle antibiotic resistance, the type of AMR that is the most pressing concern for human health. China is estimated to be the second largest consumer of antibiotics in the world, with widespread and often inessential use in both humans and livestock. Widespread consumption leads to antibiotic residues in water and soil that may exacerbate the development and transmission of resistance through organisms and chemicals in the environment. Studies have investigated the epidemiology and pattern of drug-resistant infections in China, but the size of the health and economic burdens caused by ABR on a national level and the role of the environment in the development and transmission of drug resistance are still unclear.

Most ABR research in China has focused on specific bacteria in hospital patients, selected food animals, or isolated determinants. Better evidence and broader understanding of environmental, community, economic and health care drivers and burdens of ABR based on a systems perspective that recognises interactions between these areas is urgently needed, as are evaluation tools to measure the effectiveness of different ABR-reducing intervention strategies. Due to a dense population, an intensive livestock breeding industry and massive antibiotic use, Eastern China is a key region for controlling antibiotic use and ABR. Our research aims to bridge these key evidence gaps and strengthen disciplinary and methodological research skills, through a set of closely linked projects that will generate the holistic knowledge which is needed to design, deliver and monitor targeted strategies to limit ABR in China and comparable settings. We will also establish sustainable partnerships with cross-disciplinary research expertise that is currently lacking in China and strengthen capacity in policy-relevant research. Since antibiotic resistant infections and their genetic components spread rapidly through international travel, research into ways of reducing the burden of ABR in China is important not only for populations in China and the wider Asian region, but globally.

Through three linked programmes of work based at three leading universities in China, supported by UK academics from a wide range of disciplines, we will:
1. Estimate the economic burden of AMR and determine the cost-effectiveness of potential intervention strategies
2. Design and evaluate a tailored intervention to modify antibiotic prescribing behaviour among health professionals and reduce antibiotic consumption among outpatients
3. Measure human exposure to antibiotics from environmental and livestock sources, estimate their health effects & develop tools for risk assessment and monitoring of environmental exposures to antibiotics and antibiotic-resistant genes
4. Gather evidence on current patterns of antibiotic use and the implementation of ABR-related policies and regulations at local, regional and national levels
5. Produce evidence-based recommendations on optimising antibiotic use, monitoring ABR and assessing the success of strategies to reduce ABR in China
6. Build cross-institutional and international collaborative groups to increase China's research capacity in a range of relevant disciplines and methodologies, as well as in the design and conduct of inter-disciplinary research.

Technical Summary

WP1 will develop and optimise a digital intervention to reduce unnecessary antibiotic prescribing in lower level health facilities drawing on theory, evidence and our own effective interventions. We will use participatory co-design, qualitative research with up to 60 clinicians and patients and a feasibility trial to ensure all elements of the intervention are acceptable and feasible. A cluster randomised controlled trial will then compare the intervention with usual care in 55 practices and 1642 patient consultations. The primary outcome will be reduced antibiotic usage, with non-inferiority in clinical outcomes.

WP2 comprises six linked studies in three representative areas of East China, to gather evidence on and analyse the inter-relationships between antibiotic use, occurrence and transmission of ABR in the environment, animals and humans. The studies will include assessment of antibiotic exposure in population cohorts from survey and urine (n = 3,300) and identification of types and frequencies of ABR genes in humans and food animals; analysis of antibiotic residues and ABR genes in the aquatic environment, including wastewater; mixed methods research into drivers and practices associated with antibiotic use (600 families); and analysis of the national policy context (with expert and stakeholder input) to propose strategies and systems for optimising and monitoring antibiotics use.

WP3 will estimate the health and economic burden of ABR in China and the cost effectiveness of different antibiotic-reducing interventions. The analysis will draw on national surveillance data, published literature, a prospective observational cohort study in 50 representative hospitals to determine rates of infection, resistance, length of stay, mortality and cost and findings from WP1 and WP2. A decision analysis model will be developed to determine the costs and health effects of antibiotic exposure, resistant infection and different prescribing interventions.

Planned Impact

Beneficiaries of the research
This research will inform policy and practice to reduce ABR, which will benefit people living in China, Asia and to some extent globally. ABR is known to be a significant burden to the health and economic wellbeing of people in China and other LMIC. Our work will generate evidence of i) effectiveness and cost effectiveness of an intervention to reduce antibiotic prescribing and demand; ii) environmental transmission pathways and priority targets for limiting antibiotic exposures; and iii) the magnitude of the ABR burden and cost-effective strategies for reducing it. Resulting policy and practice recommendations will help to inform behaviour, service, system and regulatory changes. This will have a potentially transformative effect on control and prevention of ABR infections in China and is likely to be transferable to other LMIC settings. As ABR is spread rapidly through international travel, reducing ABR in this region will reduce global transmission.
Our collaborative work will strengthen the research links between China and UK, promote the exchange of expertise and produce internationally excellent research. The UK team will contribute their expertise in research methods (especially large anthropological studies, observational studies, environmental and wastewater epidemiology and behaviour change intervention design) and support the China partners through training and joint research activities. This will enable the collaborating partners to develop their ABR research programmes, which will benefit both researchers and research users in China in the longer term.
Engagement activities
Throughout the research project we will involve key stakeholders with roles in managing antibiotic use, antimicrobial stewardship and reduction of ABR in humans, food animals and the acquatic environment. Research findings will be translated into short policy briefings with recommendations tailored to fit with existing policies in China and to influence current practice in health care, agricultural and urban settings. The credibility of research findings will be indicated to stakeholders through peer-reviewed publications in internationally recognised journals and presentations at academic conferences in China, the UK and internationally. We will develop context-appropriate strategies to engage wider publics through digital and other media. At the end of the project we will host a meeting for all relevant stakeholders, at which we will present (and disseminate) summaries of the research and where we will (in partnership with stakeholders) establish how our results are best implemented.
Anticipated benefits
We anticipate the proposed research will inform the design of future antibiotic stewardship (ABS) interventions as well as the research to evaluate these interventions, and improved strategies both to optimise antibiotic use and to monitor ABR. WS1 aims to produce an effective intervention to reduce antibiotic use for RTI by at least 10% that can be easily implemented nationwide. WS2 will indicate specific livestock industries where ABR gene transmission to employees and thence to the wider population is particularly prevalent, enabling government and local authorities to prioritise the improvement of farm management and food preparation practices to minimise risks. WS3 will provide the first robust estimates of the national burden of AMR and cost-effective interventions to reduce it, enabling ABS implementing agencies to maximise the efficiency of health care resource use. Improved ABS in health care contexts will reduce the number of patients suffering side effects from unnecessary antibiotics and increase the number of health care workers and institutions able to meet antibiotic prescribing regulations. Reduced antibiotic prescribing to humans and reduced transmission from livestock and water sources will reduce the prevalence of ABR infections, with potential to transfer these benefits across Asia.

Publications

10 25 50
 
Description The Economic Burden of AMR in China - A case study of Carbapenem-resistance Enterobacteriaceae
Amount ¥550,000 (CNY)
Funding ID 81973294 
Organisation National Natural Science Foundation of China 
Sector Public
Country China
Start 01/2020 
End 12/2023
 
Description Research Collaboration Agreement with Peking University 
Organisation Peking University
Country China 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution As CHINA PI and also a co-PI to this UK-CHINA AMR Hub Programme awarded by UKRI-MRC & CHINA NSFC, Peking Uni is not only assisting the coordination of hub programme, but also providing intellectual inputs, expertise and taking a lead in the national surveillance system (CARSS & CAS) data extraction and processing, national level hospital sampling, health economic data modelling of work package 3.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in the disciplines including epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description Research collaboration agreement with Anhui Medical University 
Organisation Anhui Medical University
Country China 
Sector Hospitals 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution As Co-PI to this UK-CHINA AMR Hub Partnership Programme awarded by UKRI-MRC & CHINA NSFC, Anhui Medical University is also providing intellectual inputs, expertise in the development of intervention trial design and data collection tools, also will take a leading role in implementation of intervention trial, data collection of work package 1.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description Research collaboration agreement with Fudan Univeristy 
Organisation Fudan University
Country China 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution As Co-PI to this UK-CHINA AMR Hub Partnership Programme awarded by UKRI-MRC & CHINA NSFC, Fudan University is providing intellectual inputs, expertise in the development of household cohort study design and data collection tools, environmental sampling design & analysis and stakeholder policy interviewing design, will take a lead in the cohort study data collection & analysis, the environmental sampling collection and data analysis, policy interviewing of work package 2.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with IEH consulting 
Organisation IEH Consulting
Country United Kingdom 
Sector Private 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution Prof Jason Weeks is providing environmental risk analysis and monitoring, AMR-related registration related to WP2
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with collaborating institutions 
Organisation North Bristol NHS Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution North Bristol NHS Trust is providing expertise in the microbiological analysis supports to WP2
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with collaborating institutions 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution Public Health England is providing expertise in the epidemiological supports across WPs.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with collaborating institutions 
Organisation University of Bath
Country United Kingdom 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution University of Bath is providing expertise in wastewater epidemiology (sampling sites selection, sampling design), and pathogen genomics and bioinformatics to work package 2.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with collaborating institutions 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution University of Leicester is providing and building methodological expertise in health economics, epidemiology and intervention evaluation across the three WPs including cost-effectiveness studies for the WP1 clinical trial; economic and epidemiological cost estimates for environmental exposures to ABR in WP2; and ABR burden estimation in hospital and outpatients in WP3.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description UoB Research collaboration agreement with collaborating institutions 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution UoB is leading the UK-CHINA AMR Partnership Hub together with Peking University (Beijing, China), collaborating with Anhui Medical university (Hefei, China), Fudan university (Shanghai, China), University of Bath, University of Southampton, University of Leicester, Public Health England, North Bristol NHS Trust; to strengthen cross-disciplinary research skills at different institutions between China and the UK; and formulate evidence-based recommendations to reduce antibiotics prescribing and consumption, monitor ABR in the community, and provide rational strategies to reduce the economic burden of AMR in China. UoB team are taking a lead in the coordination and management of hub programme. We are also providing research leadership, intellectual input and specialist expertise in research areas and disciplines, particularly medical anthropology, behavioural and other social sciences, qualitative methods, intervention design and evaluation related to work package 1, household cohort study design, stakeholders interview development related to work package 2.
Collaborator Contribution University of Southampton is providing expertise in the intervention trial design, statistical analysis & trial sample size calculation, qualitative evaluation in the implementation of WP1 trial; and oversee study quality in WP3, decision analytical model project for WP3.
Impact This is a multidisciplinary collaboration and we are aiming to enhance research capacity in epidemiology, health economics, anthropology, behavioural and other social sciences, qualitative methods, health systems and policy research, environmental risk assessment, cross-compartmental genomic analysis, intervention design and evaluation, and interdisciplinary research.
Start Year 2019
 
Description Annual Hub Meeting 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact The China PIs, Bo Zheng & Luwen Shi orgainzed the 1st Annual Hub Meeting in Beijing in Apr 2019; most colleagues working on this project, from China & the UK, attended this meeting.
Year(s) Of Engagement Activity 2019
 
Description Bristol AMR Symposium 2019 - Poster presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The PI, Prof Helen Lambert gave a poster presentation "Strategies to reduce the burden of antibiotics resistance in China:UK-CHINA AMR Partnership Hub (2019-2022)"
Year(s) Of Engagement Activity 2019
 
Description Hub Programme Website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact UoB team developed a Hub website to share the hub programme update, research outputs to a wider audience
Year(s) Of Engagement Activity 2020
URL https://www.bristol.ac.uk/population-health-sciences/centres/uk-china-amr-partnerships-initiative/
 
Description Partnerships to tackle the global challenge of AMR: China-UK AMR Workshop 2019 - Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The PI, Helen Lambert gave a talk " Stratigies to reduce the burden of antibiotics resistance in China
Year(s) Of Engagement Activity 2019
 
Description Peking Uni - press release about the UK-CHINA AMR Partbnerships Hub 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Peking University also published the lauched meeting of UK-CHINA AMR Partnerships Hub
Year(s) Of Engagement Activity 2019
URL http://bynews.bjmu.edu.cn/xxdt/203927.htm
 
Description Training on Cross-Disciplinary Research Design and Methods 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact The PI, Helen Lambert and other co-PIs orgainzed a one-day cross disciplinary AMR research workshop in Beijing (Apr 2019)
Year(s) Of Engagement Activity 2019
 
Description UoB Press release about the UK-CHINA AMR Partbnerships Hub 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The University of Bristol published the news for the 1st Annual Hub Meeting and also introduced the UK-CHINA AMR Partnerships Hub Programme to the schools and general public
Year(s) Of Engagement Activity 2019
URL http://www.bristol.ac.uk/news/2019/may/uk-china-amr-hub.html