The dynamics of antimicrobial resistance gene prevalence on a commercial pig farm: implications for policy

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

There is considerable concern regarding the increasing threat to human health from drug resistant bacterial infections. The major driver for the development of these drug resistant infections is the use of antibiotics in humans and animals. Each time an antibiotic is used, a wide variety of bacteria including pathogenic ('bad'), commensal ('good') and environmental bacteria will be killed by the drug, however some of these bacteria will survive because they will have become resistant to the antibiotic used. Bacteria can become resistant either through a random change in their genes (mutation) or by acquiring a new gene(s) from another bacteria (horizontal gene transfer). The ability of bacteria to share antibiotic resistance genes is of considerable concern as it is possible that commensal and environmental bacteria could act as a reservoir of resistance genes that could be acquired by pathogenic bacteria. The more antibiotics that are used, the more likely it is that these resistance genes will become established within a broad range of bacteria and environments.

Approximately 590 tonnes of antibiotics are used in humans and 420 tonnes in animals in the UK each year. Accurate data regarding use in animals is not available, however poultry and pig farming represent a significant proportion of this use. Whilst the use of antibiotics as growth promoters is banned in the EU, they are still used for group level treatments of farm animals. Our understanding as to how antibiotic use in farm animals relates to the levels of antibiotic resistance genes within different farming systems is very simplistic. We do not know how management decisions on farm impact on the diversity of the commensal and environmental bacteria on the farm and how this relates to the 'quantity' of antibiotic resistance genes in this system. We also do not understand what happens to these resistance genes in the face of different antibiotic treatment protocols, whether some protocols are 'worse' than others at selecting for resistance and whether the levels of resistance genes decay when antibiotic treatment is stopped. We therefore do not have a clear evidence base as to the most effective way to reduce and refine antibiotic use on farms to minimise selecting for antibiotic resistance genes.

The aim of this work is therefore to demonstrate that changes in the diversity of bacteria and 'quantity' of antimicrobial resistance genes within pig faeces and their environment can be measured and related to one another, antibiotic use and management changes on the farm. The application of this work will be to develop a framework with which changes to both management practices and antibiotic use on farms can be proposed that minimise the selection for antibiotic resistance. This will benefit farmers by reducing the likelihood of selecting for resistant bacteria that infect farm animals and society more generally by reducing the likelihood that antibiotic resistant infections in humans will develop as a consequence of antibiotic use in farm animals.

Planned Impact

This work will benefit the following stakeholders as follows:
- Veterinary surgeons: the ability to understand how management practices and the use of antimicrobials on farms impacts on the degree of antimicrobial resistance on a farm will provide livestock veterinary surgeons with a framework that can be used to develop guidance, antibiotic treatment protocols and management practices that ensure the judicious and responsible use of antibiotics. The responsible use of antimicrobials is a professional requirement for all veterinary surgeons as stipulated by the Royal College of Veterinary Surgeons.
- Livestock farmers: guidance as to how to minimise the development of antimicrobial resistance on farms will allow livestock farmers to adhere to management practices that protect public health and demonstrate that it is avoiding practices that could potentially be harmful to human health.
- Members of the public: reducing the selection for antimicrobial resistance in farm animals will reduce the likelihood that drug resistant human infections will develop as a consequence of antimicrobial use in farm animals. This will benefit the wider public by reducing the risk of difficult to treat human illnesses developing due to agricultural practices.
- Early career research scientists: this project proposes two post-doctoral research posts for PhD students at the Roslin Institute and Scottish Rural College. They will benefit from the opportunity to progress their career development in a world leading research environment.

Publications

10 25 50
 
Description We have described the phenotypic antimicrobial resistance profile of environmental samples collected from an intensive commercial pig unit during a standard production cycle. We have also analysed the change in environmental antimicrobial resistance gene prevalence and microbiotal diversity during this production cycle and in response to in feed antibiotic administration. This has involved developing qPCR assays for this work and bioinformatics pipelines for the analysis of this data. The most striking finding was that the copy number of key AMR genes within the farmed environment did not change in response to in feed antimicrobial administration. There was also no correlation between AMR gene prevalence and microbiotal richness and diversity. Whilst further work will be required to understand why this is the case, it is our hypothesis that the system in question (a high antibiotic usage pig farm) was saturated with the AMR genes studied in this study and the microbiota already adapted to antimicrobial administration.
Exploitation Route Our assays and protocols have been used by Adrian Muwonge (BBSRC FLF) in his project looking at antimicrobial resistance in pigs and humans in Uganda. The findings from the study farm have been fed back to the farmer and their veterinary surgeon, who are looking to extend the research undertaken in this project to understand the impact of different antimicrobial treatment regimens on the pig's microbiota and antimicrobial resistance. We are currently in discussions with a large pig feed manufacturer as to how our findings could be applied to different dietary manipulations on commercial pig units.
Sectors Agriculture, Food and Drink

 
Description This study involved the recruitment of a commercial pig farm. We worked with an industrial partner to identify and recruit this farm. The entire research group met with the farm owner and their veterinary surgeon to discuss antibiotic resistance and the objectives of the project. The farm owner is particularly active within the politics/lobbying of the pig farming industry. Whilst we are still finalising the publication from this project, our activities in explaining the context and objectives of the project has been one of the factors that has motivated the farm in question to review their antibiotic usage policy. Whilst very cautious and suspicious of our involvement with their farm at the start of the project, the farm owner has become increasingly interested in the results that may result from this study and engaging with the subject of antimicrobial resistance.
Sector Agriculture, Food and Drink
Impact Types Cultural

 
Description AHDB Beef Medicines Expert Working Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Blaxter Award
Amount £1,100 (GBP)
Organisation British Society of Animal Science 
Sector Learned Society
Country Unknown
Start 11/2016 
End 11/2017
 
Description Development of an Integrated Neonatal Survival and Sustainable Antibiotic Plan 
Organisation Agricultural and Horticulture Development Board
Country United Kingdom 
Sector Public 
PI Contribution I am PI and project manager for an AHDB funded project that started in September 2018 in collaboration with Liverpool, Nottingham and Bangor Universities and Synergy Farm Health. This two year project will determine disease and antibiotic usage during the neonatal period in lambs and suckler calves in the UK and will lead to the development of an industry wide control plan designed to reduce mortality, morbidity and antibiotic usage during the neonatal period.
Collaborator Contribution AHDB - funder, distribution of farmer surveys, training and delivery of the Neonatal Survival and Sustainable Antibiotic Plan Synergy Farm Health - recruiting and surveying farmers, pilot testing of the Neonatal Survival and Sustainable Antibiotic Plan Liverpool University - recruiting and surveying farmers, risk factor analysis, pilot testing of the Neonatal Survival and Sustainable Antibiotic Plan Nottingham University - recruiting and surveying farmers, pilot testing of the Neonatal Survival and Sustainable Antibiotic Plan, knowledge exchange from previous experience of developing similar control plants (e.g. DairyCo Mastitis Control Plan) Bangor University - analysing the effectiveness of the control plan following implementation on pilot farms
Impact None, project in development phase.
Start Year 2018
 
Description Quantifying antimicrobial use on British beef units 
Organisation University of Bristol
Department School of Veterinary Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Through the NERC funded meetings, we have developed a collaboration with the University of Bristol to quantify and benchmark antimicrobial usage on British beef units. Whilst a different livestock sector to that funded by this project, it has been identified as a part of the industry where even a basic understanding of antimicrobial is lacking. We are coordinating the collation and analysis of data from a number of different veterinary practices, which we anticipate will be representative of the UK beef population.
Collaborator Contribution Our partners will be contributing data from their own veterinary practice, as well as providing invaluable input into the analysis and interpretation of this data.
Impact Manuscript currently in preparation.
Start Year 2017
 
Description AMR 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 Contributed a presentation of the project and preliminary findings to the relevant researchers in the Scottish Government's Strategic Research programme.
Year(s) Of Engagement Activity 2017
 
Description Antimicrobial resistance lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact To raise awareness of antimicrobial resistance and its relevance to veterinary practitioners, four short presentations were embedded into lectures in the 4th year veterinary undergraduate Integrated Clinical Course: Farm Animal. These presentations were delivered by the post-doctoral research assistants to a group of approximately 170 students and focussed on the following learning objectives:
• Understand the importance of antimicrobial resistance to animal and human health
• Describe the role of the veterinary surgeon in the stewardship of antimicrobials
• Evaluate the evidence underpinning the impact of antimicrobial use in animals on human health
• Interpret data relating to antimicrobial use at a local and international level
• Appraise assays and technologies for the qualitative and quantitative assessment of antimicrobial resistance

The presentations were distributed across different subject areas within the course, including calf pneumonia, bovine mastitis, farm animal therapeutics and pig medicine. By creating an 'AMR theme' within the course that was delivered by active research scientists, the students were exposed to views and experiences of early careers researchers "at the coal face" of AMR research, in a manner that integrated with their core subject material and tied the relevance of the underlying science into their future clinical practice.

One of eight short answer questions in the end of course assessment exam, asked the students to advise a client with a supermarket contract, how they could reduced antibiotic use in the treatment of calf pneumonia. The answers given by the majority of the cohort demonstrated that they were able to incorporate the principles given to them in these short presentations into the clinical-based scenario of the question.
Year(s) Of Engagement Activity 2016,2017
 
Description Responsible antibiotic use on beef farms webinar 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Two webinars delivered for AHDB Beef and Lamb on the responsible use of antibiotics on beef farms. The key message was to avoid the use of the highest priority critically important antibiotics and to address underlying management and disease problems that result in diseases requiring antibiotic treatment. One webinar was delivered to veterinary surgeons and the other to farmers, with an estimated audience of 100-150 people in total.
Year(s) Of Engagement Activity 2018
URL https://youtu.be/yXaYIaJ0efs