Acquisition and Selection of Antibiotic Resistance in Companion and Farmed Animals and Implications for Transmission to Humans

Lead Research Organisation: University of Bristol
Department Name: Cellular and Molecular Medicine

Abstract

Without antimicrobial drugs, the risk of bacterial infection would render many common medical procedures too dangerous to contemplate because of the risk of infections caused by "opportunistic bacteria". They can live on the patient's skin, or in their intestines, and infection occurs when bacteria get into parts of the body that are normally sterile. A perfect example is urinary tract infection (UTI) caused by faecal bacteria. E. coli is particularly abundant in human faeces so is perfectly placed to cause opportunistic infections. It is one of the most common causes of healthcare pneumonia, surgical site infection, bloodstream infection and UTI in the UK. In order to prevent against and treat opportunistic infections, patients are given antimicrobials.

Almost all antimicrobials are "antibiotics", which means they are derived from natural chemicals produced by microbes found in the environment. Natural antibiotics have been present in the environment for millions of years, and so bacteria living in their presence have had time to evolve mechanisms that can resist their actions, encoded by "resistance genes". Opportunistic bacteria like E. coli can randomly acquire these pre-evolved resistance genes and in a single step, they become insusceptible to a particular antimicrobial. If that insusceptible E. coli colonises a person and then causes an opportunistic infection, the infection will not be treatable with that particular antimicrobial. We refer to this as "antimicrobial resistance" (AMR); however AMR bacteria don't just resist clinical antimicrobial therapy, they beat it.

Animals also carry an abundance of E. coli in their intestines and are frequently treated with antimicrobials. This can select for the acquisition of AMR E. coli which can then be passed on to another animals, directly, or via contamination of the environment with faeces. Theoretically, the AMR E. coli could also be passed on to people, and there is much debate about whether such "zoonotic transmission" happens to any significant degree. This is an important debate because it has led to calls from some to dramatically reduce the amount of antimicrobials that are given to animals with the view that it will reduce the level of AMR in animals, and so the possibility of zoonotic transmission to people. But the potential impact on welfare and food production means this should only be done if there is evidence that it will work.

In this project we will identify what drives acquisition of AMR in animals using E. coli as the exemplar bacterium and dairy cows and dogs as exemplar farmed and companion animals. We will test whether AMR bacteria encountered by an animal as it interacts with the environment influence the AMR profile in its faeces, and/or whether early life antimicrobial use plays a part in selection of AMR bacteria in animals. We will also test whether reducing antimicrobial use in dairy cows actually does reduce AMR in the near-farm environment that is contaminated with their faeces. We will test whether exercising in these contaminated near-farm environments influences the abundance of AMR bacteria in dogs, and whether there is any evidence of direct acquisition of AMR E. coli by dogs from near-farm environments, which might be brought into the home.

Finally, we will investigate whether AMR abundance in human UTI E. coli reduces as antimicrobial drug prescribing reduces in primary care; whether living close to a farm affects AMR abundance in UTI E. coli; whether there is direct evidence for E. coli carried by dogs or found in near-farm environments contaminated by cattle faeces also causing UTIs in humans.

These interlaced studies will provide much needed data about the management changes that might reduce AMR in animals and in humans, and are designed to address the fundamental question of whether zoonotic transmission is particularly significant as a driver of AMR in people relative to antimicrobial drug use by doctors.

Planned Impact

INDUSTRY
This project addresses the impact that the Farming and Veterinary Medicine industries might have on human health through animal-mediated contamination of publically accessible land with AMR bacteria, and because zoonosis is a recognised health and safety risk for farmers and veterinarians. Understanding risk factors for acquisition of AMR in farmed and companion animals and possible ways to mitigate them will help these industries react to growing public concern about AMR and possible legislation in an informed way. Directly involving businesses from these sectors in our project will allow them to advocate for our findings in their own industries. For example, provision of first-hand evidence on the positive effect of reducing antibiotic use on AMR levels on the farms in our study may stimulate a peer-led process to encourage other businesses to consider how to reduce levels further. Limiting the rise of AMR will make farming in the UK more productive (via less untreatable disease) and more economically successful, and will provide a model for tackling AMR elsewhere in the world.

REGULATORY BODIES
The Veterinary Medicines Directorate (VMD) has confirmed its interest in this project, and we have had meetings with the VMD AMR Surveillance Team about our work. VMD is responsible for channelling EU regulations for reducing AMR in the veterinary controlled environment. VMD recognise, however, that there are significant knowledge gaps, and this study will address three of these: how antibiotic use selects for resistance; current AMR levels in healthy animals and in the environment; what might be done to reduce these levels. Other Defra executive agencies such as Natural England are likely to be interested in our research as it pertains to footpaths and we have included significant Public Health England involvement in the project, so our findings can feed back to provide public information about the importance of reducing exposure to AMR in the environment. Local authorities also have responsibility for establishing areas in which dog faeces must be collected and enforcing bylaws, so the may also be interested.

THIRD SECTOR
Approximately 130,000 dogs were estimated to enter rescue centres run by animal charities in 2009. Dogs mixing in these environments may be an important aspect of AMR transmission, impacting on the management of such centres. Charities also place dogs into new homes (e.g. Dogs Trust re-homed almost 15,000 dogs last year), and information on risk to human health from this project will help inform the best policy. Walking groups including those convened through the Ramblers' Association and the U3A will be interested in the findings of this study. U3A members are likely to be aware through personal experience of the rise of AMR and its role in healthcare-associated and opportunistic community infections, and may benefit from any simple risk mitigation strategies that our findings might suggest.

WIDER PUBLIC
According to Natural England, >800 million visits to the natural environment were made by people in England and Wales between March and May 2015. An estimated 10.5 million dogs are kept as companion animals in the UK, and are often regarded as members of the family. If zoonotic transmission of AMR from the environment, directly or via companion animals, is a significant health risk, then our research promises considerable benefits for the health and wellbeing of the UK population by attempting to identify risk factors for acquisition of AMR in farmed and companion animals, but also by simply highlighting such a risk. For instance, basic hand hygiene is a simple intervention that might be all that is required to have a considerable effect on decreasing the transmission of AMR pathogens.

Publications


10 25 50
 
Description Guideline Development Group for the NICE 'Managing Common Infections' Guideline - Alastair Hay
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
URL https://www.nice.org.uk/guidance/indevelopment/gid-ng10050/documents
 
Description RUMA Scientific Committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description AMR talk at Monkton Coombe School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Matthew Avison visited Monkton Coombe School to give a talk on AMR entitled 'Superbugs: Is Resistance Futile?' Pupils came up with imaginative questions and the school reported increased interest in the subject within the school population.
Year(s) Of Engagement Activity 2017
 
Description Access to Bristol schools event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact About 50 motivated college students came to Bristol from the region to get a taster for microbiology. Matthew gave a talked entitled Superbugs: Is Resistance Futile? Some students reported it had given them an interest in going into the field of microbiology.
Year(s) Of Engagement Activity 2016
 
Description Alastair Hay - University of Washington School of Medicine Research Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Alastair was invited to speak at the University of Washington to present "Improving Use of Antibiotics for Children in Primary Care - International Research from the United Kingdom". Faculty staff and junior doctors discussed how educational practitioners should be educated in policy and feedback was that lessons Alastair has learnt will be useful for our US counterparts.
Year(s) Of Engagement Activity 2016
URL https://depts.washington.edu/fammed/blog/dfm-research-seminar-improving-use-of-antibiotics-for-child...
 
Description American and Canadian High School visit to UoB 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Pupils from American and Canadian High Schools attended a day at UoB. Matthew gave a talk entitled Superbugs: Is Resistance Futile? Pupils had many challenging questions and some said afterwards that they had no idea you could select for an antibiotic resistance gene by using another antimicrobial like ammonium compounds.
Year(s) Of Engagement Activity 2016
 
Description Award Press Release - University of Bristol 
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 Media (as a channel to the public)
Results and Impact Press release about the award and its aims. Several news outlets picked this up.
Year(s) Of Engagement Activity 2016
URL http://www.bristol.ac.uk/news/2016/june/animals-humans-amr.html
 
Description BBC Radio Bristol Interview 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Matthew Avison had 30 minute interview with Steve Yabsley on BBC Radio Bristol about AMR research project. Stimulated discussion via phone in comment from members of the public
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/programmes/p04dxl57
 
Description BridgeBridge AMR Schools Outreach Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 160 students from the region came to a cross-faculty schools conference recently for post-16 biology and chemistry students held within the School of Chemistry to examine why AMR is an escalating global threat. Matthew opened the conference and gave a talk entitled 'Superbugs: Is Resistance Futile?'
Year(s) Of Engagement Activity 2016
URL http://www.bristol.ac.uk/news/2016/december/schools-conference-amr.html
 
Description Bristol Grammar School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Matthew Avison gave a talk entitled 'Superbugs: Is Resistance Futile?' to Bristol Grammar Senior School pupils. Pupils gave feedback such as "I used to think antibiotics were normal when you have a bad cold but I now know it's more likely to be a virus so will only use them if I have to."
Year(s) Of Engagement Activity 2017
 
Description Bristol Health Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Matthew gave a talk to over 100 members of the general public during a session called Bristol Love Bugs. His talk was about the Impact of Antibiotic Use on the Microbiome.
Year(s) Of Engagement Activity 2016
URL http://www.bristolhealthpartners.org.uk/events/view/2016/10/22/bristol-loves-bugs-the-human-microbio...
 
Description Bristol Tackles Global Challenges World Café 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Matthew Avison and Kristen Reyher gave presentations on their work and discussed potential areas of collaboration in the future with researchers from the UK as well as abroad, including many delegates from Thailand. Many interesting ideas came from this week of talks and workshops.
Year(s) Of Engagement Activity 2017
URL http://www.bristol.ac.uk/bristolbridge/events/2017/bristol-tackles-global-challenges.html
 
Description Cheltenham Ladies' College - talk on AMR 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Matthew Avison gave a talk called "Superbugs: Is Resistance Futile?" to 90 students at Cheltenham Ladies College. This talk provoked questions and debate about AMR and Matthew was also approached by students afterwards with further queries.
Year(s) Of Engagement Activity 2017
 
Description Filton College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Matthew gave a talk entitled 'Superbugs: Is Resistance Futile?'. Response was good and some students asked about careers in microbiology.
Year(s) Of Engagement Activity 2016
 
Description Gave talk at Sidmouth Science Festival 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact About 100 members of the general public attended my talk, "Superbugs: Is Resistance Futile?". Feedback included surprise at "cross resistance caused by biocides," that "antibiotics occur in soils" and "how long E.coli can live in the body". The audience reported changed views such as "I used to think basically that the more antibiotics you used, the healthier and better prepared you were. Now I'll be more cautious."
Year(s) Of Engagement Activity 2016
 
Description Involvement in TV Documentary - Hidden Killers of the Post-War Home 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Matthew Avison participated in a BBC4 documentary produced by Modern Television in a segment about zoonotic pathogens in food and the importance of hand hygine. Significant response on social media and via BBC online fora.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/programmes/b07chyly
 
Description Langford Vets Antibiotic Awareness Evening 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact CPD evening for vets, although was also attended by a medical microbiologist and a medical pharmacist. There was much discussion between the speakers and audience, and feedback included: "As a medical microbiologist working in human health in a local hospital, I found it refreshing and very interesting to see the extent, commitment and drive to work to combat antimicrobial resistance in the animal sector - really for the greater good of population health." One vet enquired about consultancy for their practice.
Year(s) Of Engagement Activity 2016
 
Description NAMRIP/FSA joint workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Kristen Reyher gave a presentation entitled "Auditing for Responsible Antibiotic Use" at a at a Food Standards Agency/University of Southampton workshop tackling AMR and the retail supply chain.
Year(s) Of Engagement Activity 2016
URL http://www.southampton.ac.uk/namrip/news/2016/12/joint-fsa-workshop.page
 
Description News Announcement in "Farming UK" 
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 Industry/Business
Results and Impact Write-up about study aims and award details in farming press. Stimulated requests for involvement in the project from farmers and retailers/milk buyers.
Year(s) Of Engagement Activity 2016
URL https://www.farminguk.com/News/-1-5m-research-grant-allows-scientists-to-test-antibiotic-resistance-...
 
Description PHE Taunton Workshop - AMR: Working Together to Stem the Tide 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact At this event, which was organised by Public Health England, David Barrett gave a presentation on our AMR work and presented a poster on OH STAR. Feedback, both formal and informal, from the day was very positive. For example, 84% of delegates agreed or strongly agreed that national and local learning had been shared to aid the development of local AMR plans, whilst 92% of delegates felt that they developed an increased understanding of the shared national priorities for AMR.
Year(s) Of Engagement Activity 2016
URL https://www.phe-events.org.uk/HPA/media/uploaded/EVHPA/event_622/AMR_Final_Slides.pdf
 
Description Presentation to Chief Scientific Advisor Chris Whitty 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Professor Chris Whitty, Chief Scientific Advisor for the Department of Health visited University of Bristol to hear of our work and latest findings. Matthew Avison and Ashley Bryce gave presentations, and Professor Whitty sent feedback later in the week saying he'd taken our findings on board and had found the visit useful.
Year(s) Of Engagement Activity 2017
 
Description Public Health England/BSAC webinar series on antibiotic prescribing for children - Alastair Hay 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Major contribution to the creation of the TARGET Antibiotic Training Modules, along with Public Health England and BSAC. These are free open access modules to help practitioners improve antibiotic prescribing and the patient experience. These are now accredited for CPD by the Royal College of GPs.
Year(s) Of Engagement Activity 2016
URL http://target-webinars.com/
 
Description Radio 4 Farming Today - David Barrett Jan 2017 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact David Barrett talked to Farming Today about reducing antibiotics in farming.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/b088b84z
 
Description Semex International Dairy Conference Glasgow 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact David Barrett gave a talk at the Semex Conference, whose delegation is mainly farmers and associated professionals. Questions and tweets ensued, so an audience was reached far outside those hundreds present.
Year(s) Of Engagement Activity 2017
 
Description Sheldon School - AMR talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Matthew Avison gave a talk entitled 'Superbugs: Is Resistance Futile?' to 80 secondary school pupils. Students asked questions about antibiotics and resistant bacteria and the school sent good feedback about the talk.
Year(s) Of Engagement Activity 2017
 
Description South West Zoonoses Liason Group meeting - Nov 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact David Barrett was invited to talk to the South West Zoonoses Group about our AMR work at University of Bristol. This group is made up of medical practitioners and members of Public Health England. Some misconceptions of the group's medical delegates were discussed and reinformed.
Year(s) Of Engagement Activity 2016
 
Description St Lawrence School talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Matthew gave a talk entitled 'Superbugs: Is Resistance Futile?' There were many interesting questions from pupils and teachers reported the kids felt they had learnt a lot.
Year(s) Of Engagement Activity 2016
 
Description Surgeon X Comic 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Matthew Avison was asked to advise and contribute to the Surgeon X comic (Wellcome Trust Funded), which imagines a world beyond the antibiotic age, which was published via Wowbagger Productions. The comic is sold in print form and via an app. There has been significant international impact.
Year(s) Of Engagement Activity 2016
URL http://surgeonx.co.uk/our-team/
 
Description Swindon College AMR talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Matthew Avison gave a talk entitled 'Superbugs: Is Resistance Futile?' This was to inspire a new generation of microbiologists and raise awareness of AMR. Students fed back change in perceptions and increased interest in microbiology.
Year(s) Of Engagement Activity 2017
 
Description Talk at Warwick SWON Alliance Industry day. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk at the SWAN industry day to industry and academic representatives. Significant interest generated in methods for determining antibiotic action via proteomics
Year(s) Of Engagement Activity 2016
URL https://www2.warwick.ac.uk/fac/cross_fac/wamic/swon/industry/
 
Description Veterinary Record News Article 
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 Professional Practitioners
Results and Impact Announced the award and the aims of the project to veterinary professionals and stakeholders; a number of enquiries about involvement in the project were received.
Year(s) Of Engagement Activity 2016
URL http://veterinaryrecord.bmj.com/content/178/25/622
 
Description Winterbourne International Academy - school talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Parents and pupils of Winterbourne Academy attended their Festival of Science lectures, one of which was a talk by Matthew entitled "No more drugs for superbugs"
Year(s) Of Engagement Activity 2016
URL http://www.myyate.co.uk/yate/e/18972/festival-of-science-lectures