A systems understanding of the flow of Antimicrobial Resistance from livestock production to the environment and humans: informing antimicrobial stewardship and optimal use

Challenges

Antimicrobial resistance (AMR) is a major global concern to human health. AMR occurs when microbes become resistant to clinical or veterinary drugs used to treat disease. AMR has major consequences on how to manage microbial diseases and the use of antimicrobial compounds.

The UK’s National Action Plan to tackle AMR details a One Health approach to “Better understand how AMR spreads between and among humans, animals and the environment.” The action plan recognises the lack of knowledge about AMR in the environment, including:

• The relative importance of different sources

• Transmission pathways of AMR between animals and the environment

• The risks and effects for people, animals, food, and ecosystems

In 2017, the Codex Alimentarius Commission agreed to extend and expand its code of practice for food chain actors on minimising and containing AMR. The Commission set up an ad-hoc Intergovernmental Task Force on AMR. The Task Force aims to develop science-based guidance on managing foodborne AMR. Alongside strong antimicrobial stewardship, the Task Force recommended more evidence on the links between animal health and welfare, productivity, drug usage and resistance.

Bovine Respiratory Disease (BRD) is a major challenge for cattle production, and it continues to cause serious economic losses for producers. BRD control is a major target of antimicrobial usage and an important source of AMR pathogens.

However, little is known about:

• Prevalence of AMR for the main BRD pathogens in the Scottish cattle industry

• The resistome (collection of antimicrobial resistance genes) in the respiratory tract

• The link between AMR levels and dissemination of strain(s) carrying integrative and conjugative elements (ICEs), which are associated with multidrug resistance.

To achieve global knowledge of AMR in the Scottish context an understanding of the relationships of antimicrobial use and spread of AMR is required.

Questions

Solutions

Antimicrobials are often the last line of defence in protecting animal health and maintaining animal welfare standards. This project is providing a deeper understanding of the consequences of antimicrobial use in livestock production to extend the useful lifespan of individual antimicrobials and reduce risk to public health and the wider environment.

Quantifying the AMR gene profiles of livestock and linked environments

We are characterising and quantifying the AMR gene profiles of co-located pig and beef production units and their environments (soil, wildlife, farm workers, and water courses) using a bottom-up system approach that uses the Easter Howgate farm as a worked example. This activity compares the AMR gene carriage of the microbiomes and E. coli isolates (AMR gene presence, richness, diversity, and phenotypic resistance). Escherichia coli is a commensal bacterium present in the gastro-intestinal tract of humans and animals. This bacterium is considered a non-pathogenic indicator of AMR as it is naturally susceptible to almost all relevant antimicrobial agents, and is inherently able to accumulate resistance genes, including transferred from other bacteria. These AMR gene profiles complement the AMR gene counts quantified in a complementary project.

Analysing the Relationships between antimicrobial use at a population level and phenotypic AMR in Scottish livestock

Food Standards Scotland (FSS) and SRUC Veterinary services monitor resistance in E. coli cultured from cattle, sheep, pigs and poultry presenting at Scottish abattoirs for slaughter (i.e., healthy animals). The E. coli isolates are tested against a panel of antimicrobials relevant to human risk, rather than veterinary practice. The reporting of the AMR test results lacks contextual information, like farm of origin or location. We are performing a descriptive analysis of the 2017-2021 national AMR data, focusing on when and where AMR has spread for pigs, sheep, cattle, and poultry. The analysis of the historic data along with the isolates collected in research elsewhere is a necessary step to study the links between the resistance patterns found and the establishment of monitoring or control plans to minimize the threat of AMR in areas or farms at risk. The analysis also places the AMR of E. coli from the pig and cattle units into a national context.

Livestock systems involve various levels of production strata (animal, group, herd). The level in which the greatest variation in AMR is found provides an indication of the factors that determine AMR in livestock systems. We are quantifying the variation in AMR across the different strata to provide an indication of what are the most important factors within the livestock system that affect AMR. Guidance on how to reduce the circulation and survival of AMR organisms by isolating animals likely to have AMR depends on estimating both the decay rate of AMR in treated animals and the transmission rate between animals in a group. We are also estimating both these parameters that describe the dynamics of AMR within a group of animals. This helps to provide policy advice to stakeholders on any effects of isolating animals that have been treated with antimicrobials to optimise their use whilst minimising the risk of AMR transfer.

Antimicrobial resistance in bovine respiratory pathogens

This activity addresses key knowledge gaps by evaluating the presence of AMR genes and integrative and conjugative elements (ICEs) associated with multidrug resistance. The presence of ICEs harbouring AMR may be significant for the effectiveness of drug therapies for the control of BRD in cattle. We are developing new diagnostic strategies for the BRD pathogens and adequate measures to mitigate the use of antimicrobial agents.

Overall, this project is providing a robust evidence base for antimicrobial stewardship and optimal use in livestock production. Understanding the consequences of antimicrobial use in livestock production will inform optimal use strategies that extend the useful lifespan of individual antimicrobials and reduce risk to humans and the wider environment.

Project Partners

Progress