Does the potential for AMR selection differ between common UK cattle grazing systems?

Lead Research Organisation: Rothamsted Research
Department Name: Sustainable Agriculture Sciences-NW

Abstract

Antimicrobial resistance (AMR) occurs because repeated exposure to antimicrobial drugs kills susceptible bacteria leaving the resistant types to multiply. Recent high-profile reports of the devastating consequences for human health caused by the resistance of disease-causing bacteria to antibiotics have emphasized the need to understand the processes that drive increasing prevalence of antimicrobial resistance in human and animal pathogens.

Farm animals are considered to be a major source of AMR because of the large amounts of antibiotics used both to treat infection (therapeutic use) and to prevent infection (prophylactic use). However, little is known about the background levels of resistance in farming systems, even when animals are only treated with antibiotics when they need them (therapeutically). For instance, the sharing of genetic material by bacteria that are in close proximity is another route where AMR may emerge unexpectedly in otherwise non-related bacteria. AMR transmission between cattle is likely to be greater when they are close together, for example during the winter housed period. In this proposal we will use an experimental farm where cattle being raised for beef production only receive minimal antibiotic treatment described as 'best practice' by vets. We will monitor dynamics of AMR bacteria and genes in cattle dung in summer when the cattle are grazing in the field, and in the winter when they are housed together. We will carefully monitor cattle who have been sick and have been given antibiotics and those in the rest of the herd.

The diet of farm animals may also effect increased AMR in their gut flora. Even common plants ('forage') like grass and clover that cattle commonly eat when they are out grazing produce natural antimicrobial compounds that may continue to be active in the stomach (rumen) where millions of bacteria thrive and multiply. In the winter, cattle are brought indoors and fed silage which is grassland plants that have been fermented to conserve them. Undigested diet and lots of bacteria from the rumen, and therefore perhaps AMR, are excreted in cow dung. We will analyse the dung of cattle that eat different forage types to find out if what they eat affects the likelihood of AMR arising in cattle fed one diet compared to another.

Most cattle farming in the UK is situated in the hilly 'wet West' where the potential for rain to runoff fields into waterways is high. Recent increases in storms that cause lots of runoff and flooding may be due to climate change, are predicted to continue. At the same time, in recent years there has been an increasing recognition that AMR may arise in farm animals and be released from the farm environment to the natural environment in water and might therefore end up in drinking water, bathing water or in seafood. Normally, pollution from cattle dung in water is monitored using faecal indicator organisms (FIOs), which are bacteria that do not usually cause disease but which correlate with those that do (pathogens), and can be handled safely by scientists. It would be useful to know what proportion of FIOs carry AMR, because they are routinely tested for, facilitating estimates of AMR transmission to be estimated in the future. We will sample water flowing from fields that have been grazed by beef cattle or spread with their manure, and analyse the bacteria in the water including the FIOs to see if they are resistant to antibiotics.

The results of this study should help us to understand whether AMR that arises in cattle herds may be transferred to the environment, whether management can limit AMR and its transport, and inform approaches for assessing risks of new antibiotics and managing adverse effects that might be occurring. It is important work for addressing risk in our complex agro-food system that is clearly important for both consumers and farmers.

Planned Impact

The emergence of disease-causing bacteria that are resistant to antimicrobial compounds (typically antibiotics) threatens the global human population. Practicing medics and vets who rely on antibiotics to treat disease in humans and animals will benefit from the new evidence that this project will provide on the baseline levels of AMR in common farming systems in the UK to inform their selection of therapeutic drugs.

This research will determine the levels of abundance and the potential transport of antimicrobial resistance (AMR) from food animals (beef cattle) into waterways in grasslands used for livestock production, so will inform all agencies concerned with risk management in farming systems, including Defra and ADAS.

Grasslands cover 65% of all available agricultural land, and are concentrated in the 'wet West' often on sloping ground with heavy, easily waterlogged soils. Therefore, the trend for increased and intense pulses of rainfall in the region due climate change also raises the potential for movement of waterborne disease-causing bacteria and AMR from dung from grazing animals and manures into waterways and the potential contamination of drinking water supplies. By investigating the effect of management alternatives for forage production at the farm-scale, this project will also provide evidence of how hydrology may be changed and influence the movement of waterborne disease-causing bacteria (indicated by faecal indicator organisms, FIOs) and AMR, of benefit to water companies and the Environment Agency.

Livestock farmers are being blamed for contributing to AMR in the clinic through the overuse of antibiotics, particularly when used prophylactically to prevent rather than treat disease, but drugs are expensive so strategies for reducing disease overall are preferred. Best practice, reactive use of antibiotics is common in British beef farming, so the selection for drug resistance should be much less compared to dairy farming, for example. However, other types of non-drug related antibiotic resistance may arise in beef cattle systems, because forage naturally contains anti-microbial compounds (e.g. phenols) which may cause selection of AMR in the rumen which is excreted in dung into the environment. The close proximity of housed animals may also increases the likelihood of dissemination of AMR bacteria between animals in the same herd in the winter, this will be studied during a summer pasture, winter housed management cycle. This project will determine whether different management of forages affect the potential for AMR to emerge in beef cattle herds, and whether the transfer of disease-causing bacteria and AMR in cattle can be reduced by altering diet.

Publications

10 25 50
 
Description We have been sampling and analysing dung from our beef cattle herd on the North Wyke Farm Platform over time looking at two different cohorts, to see if any bacteria will grow in the presence of (I) antibiotics that we have used therapeutically: Tetracycline and Marbofloxacin, and (II) antibiotics that we have not used, including 'antibiotics of last resort': meropenem (carbapenem based) and colistin. At each sampling we are growing the bacteria, from the dung, on selective agars, looking for and counting E. coli (a faecal indicator organism (FIOs) used throughout the world in the protection of public health). • Results indicate some bacterial resistance to tetracycline • No bacterial growth observed on Marbofloxacin, Meropenem or Colistin. We have also looked at the run off from our fields to see if we can detect E.coli that are resistant to the same antibiotics. Interestingly we're not finding the E.coli that are resistant to tetracycline in our water samples. We did however, detect E.coli that were resistant to tetracycline in soil from areas of our fields were cattle tend to congregate, what we've called 'hot spots'.
Exploitation Route The results around field 'hot spots' have the potential for further investigation for implications on farm and at risk areas.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Dr Chris Hodgson, Dr Will Gaze and Professor Jennifer Dungait spent a day in February 2017 with a BBC film crew contributing to a science documentary for BBC4 called "Resistance Hunters" (working title) with the following spec: The increasing resistance to antibiotics of many strains of pathogenic bacteria is one of the greatest international challenges of the 21st century. Dr Michael Mosley MD is known for his immersive approach to scientific discovery. During the film, he'll make visible the world of microbial resistance with help from a life-size version of himself, a microbial twin created in a laboratory from swabs of his own bacteria grown on an agar model. It will be the first time that anyone has replicated a human biome in a petri dish on this scale. Outside of the lab, we'll meet people around the world who are searching for new ways to understand how resistance develops and to help combat the diminishing returns of our current stock of antibiotics - from doctors on the front line, to microbiologists trying to unlock the mysteries of millennia-old bacterial resistance deep underground in New Mexico. We'll explore the new techniques being developed for faster diagnosis, more targeted drug use and novel antibiotic discovery, to highlight the need for a multifaceted approach to the antibiotic resistance crisis.
First Year Of Impact 2017
Sector Agriculture, Food and Drink,Environment,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description ? Invited to meeting in South America (Argentina or Uruguay in June 2018) to advise the Interagency Coordination Group on Antimicrobial Resistance (IACG) co-chaired by the UN Deputy Secretary-General and the Director General of the World Health Organization.
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Co-authored a box in Chief Medical Officers annual report
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL https://www.gov.uk/government/publications/chief-medical-officer-annual-report-2017-health-impacts-o...
 
Description Invited by Lee Slater (Senior Policy Advisor on AMR in the environment at Defra) to sit on a panel of academic experts in a series of workshops between the US, UK, China and India on antimicrobial resistance and antibiotic pollution in the environment. It's being co-ordinated by the UK Science and Innovation Network and the USA Centers for Disease Control and Prevention.
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Invited to speak to Defra Antimicrobial Resistance Coordination (DARC) Group Autumn 2017 on AMR in the environment.
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Talk to Defra and veterinary medicines directorate about antibiotics in the environment
 
Description Invited to speak to Defra Hazardous Substances Advisory committee about AMR in the environment
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Strategies for Addressing Antimicrobial Resistance - Future challenges for UK policy
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Antimicrobial Resistance in the Environment Partnering workshop
Amount £2,500 (GBP)
Organisation UK Aid 
Start 09/2018 
End 09/2018
 
Description AMR Force 
Organisation University of Bristol
Department School of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Attended meetings to discuss further funding opportunities
Collaborator Contribution Contributed to discussion
Impact Preparation of research ideas for further funding.
Start Year 2016
 
Description Advgisory group member for Eden Project Wellcome Invisible Worlds exhibition 
Organisation The Eden Project
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Advisory group to Invisible Worlds (£1 million Wellcome funded exhibition that includes microbiology)
Collaborator Contribution Advisory group to Invisible Worlds (£1 million Wellcome funded exhibition that includes microbiology)
Impact The Eden Project will be hosting the Programme Integration Grant (NERC Environmental Microbiology and Human Health) final meeting and we will develop a display of the NERC programme data
Start Year 2017
 
Description NERC AMR Livestock and the Environment 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Introduction to the project to the wider UK AMR research community.
Collaborator Contribution N/A
Impact Advice from partners from industry as well as academia.
Start Year 2016
 
Description ? Attended a Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) workshop in Gothenburg 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Attended a Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) workshop in Gothenburg in September 2017 to explore and identify critical research needs that relate to the environmental dimensions of AMR, both in the longer term for providing input to an updated JPIAMR Strategic Research Agenda, but also in the shorter term to provide guidance for specific calls.
Year(s) Of Engagement Activity 2017
URL https://www.jpiamr.eu/wp-content/uploads/2017/11/Report-_JPIAMR-workshop-on-Environmental-dimensions...
 
Description ? Co-authored a "box" on AMR and pollution to be included in the Chief Medical Officer's Annual Report. Summer 2017, published March 2018. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Invited to co-author a "box" on how environmental pollution drives AMR, included in CMOs annual report
Year(s) Of Engagement Activity 2017
URL https://www.gov.uk/government/publications/chief-medical-officer-annual-report-2017-health-impacts-o...
 
Description ? Gaze, W.H. Selection for, dissemination of and exposure to antibiotic resistant bacteria in the natural environment. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact 4th International Conference on Responsible Use of Antibiotics in Animals, The Hague, September 2016.
Year(s) Of Engagement Activity 2016
URL https://www.responsibleantibioticuse.org/#xl_xr_page_index
 
Description ? Invited by MRC to work with Viadynamics to develop an AMR framework to map out research challenges and ways in which we are addressing those challenges. 
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 Advise RCUK policy on research priorities on AMR
Year(s) Of Engagement Activity 2017
 
Description ? Invited to EA meeting on AMR in waste water to plan EA programme of investigation. March 2017 
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 Help inform water industry AMR research programme
Year(s) Of Engagement Activity 2017
 
Description ? Invited to Strategies for Addressing Antimicrobial Resistance - Future challenges for UK policy. Workshop organised by RAND and attended by Chief Medical Officer, Chief Veterinary Officer and Chief Pharmacist. 
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 Meeting attended by Chief Medical Officer, Chief Veterinary Officer and Chief Pharmacist plus a small number of academics and RAND to develop future UK government AMR strategy
Year(s) Of Engagement Activity 2017
 
Description ? Invited to meeting in South America (Argentina or Uruguay in June 2018) to advise the Interagency Coordination Group on Antimicrobial Resistance (IACG) co-chaired by the UN Deputy Secretary-General and the Director General of the World Health Organization. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact International policy development, UN/WHO
Year(s) Of Engagement Activity 2018
URL http://www.who.int/antimicrobial-resistance/interagency-coordination-group/en/
 
Description ? Invited to speak to Defra Antimicrobial Resistance Coordination (DARC) Group Autumn 2017 on AMR in the environment. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presentation to DARC, Defra, Veterinary Medicines Directorate, European Medicines' Agency personnel present.
Year(s) Of Engagement Activity 2017
 
Description ? Invited to speak to Defra HSAC committee about AMR in the environment. March 2017. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Providing expert advice to Defra on AMR in the environment
Year(s) Of Engagement Activity 2017
 
Description ? Met Lee Slater (Defra Senior Policy advisor on AMR and the environment) for 2.5 hours to discuss AMR in the environment. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Discussion with Defra Senior Policy Advisor on AMR in the environment
Year(s) Of Engagement Activity 2017
 
Description ? NERC Planet Earth article "Have we opened the floodgates on antimicrobial resistance?" Winter 2016/17. 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact ?Article for Planet earth detailing role of flooding and climate change on environmental transmission of Amr
Year(s) Of Engagement Activity 2017
 
Description ? Wrote UNEP Frontiers chapter on AMR in the environment and attended United Nations Environment Assembly 
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 Policymakers/politicians
Results and Impact Invited to write Chapter for Frontiers United Nations Environment Programme (UNEP) publication on AMR in the environment. UNEP led with this at media event in Nairobi and assembly committed to tackle AMR in the context of Environment and Human Health.
Year(s) Of Engagement Activity 2017
URL http://wedocs.unep.org/bitstream/handle/20.500.11822/22255/Frontiers_2017_EN.pdf?sequence=1&isAllowe...
 
Description AMR, Livestock and Environment workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Workshop to examine processes in water, soil and plants and livestock leading to the emergence of AMR in livestock farming systems.
Year(s) Of Engagement Activity 2016
 
Description Educational actvities at university. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact In a class of 12 MSc Food Security and Sustainable Agriculture students effects and costs of AMR on livestock farming was discussed hereby raising awareness of the growing global concern linked to AMR.
Year(s) Of Engagement Activity 2016,2017
 
Description Filming for BBC4 program on AMR 
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 Media (as a channel to the public)
Results and Impact Filmed with freelance program makers for a Michael Mosley BBC4 documentary on AMR
Year(s) Of Engagement Activity 2017
 
Description GW4/BristolBridge: Systems approaches to AMR in Different Environments (16 Mar 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presented outline of grant to researchers working on AMR in the environment
Year(s) Of Engagement Activity 2017
 
Description Invited Talk at the RVC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of the project at the Royal Veterinary College as part of a microbiome symposium
Year(s) Of Engagement Activity 2018
 
Description Workshop at the University West of Scotland 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented the project to the BBSRC sponsored workshop
Year(s) Of Engagement Activity 2018