Antimicrobial Resistance

The challenge of antimicrobial resistance

This explainer was written by Laura Higham of FAI Farms based on her contribution to a chapter of the book One Welfare: The Role of the Veterinarians.

Antimicrobial resistance (AMR) is amongst the most significant health threats facing human society. It is currently responsible for an estimated 700,000 human deaths per year, predicted to rise to 10 million by 2050, with a cumulative cost to global economic output of 100 trillion USD (O'Neill 2016). These impacts are due to a decline in the efficacy of antimicrobial drugs, threatening our ability to prevent and treat bacterial infections using the products that we have come to rely on in modern medicine.

Antibiotic use is a key driver of antimicrobial resistance. By using antibiotic drugs, we apply a selection pressure that kills susceptible microbes but provides the surviving drug-resistant bacteria with a competitive advantage and potential to cause untreatable disease in their human or animal hosts. Drug-resistant, multi-drug resistant and pan-resistant bacteria are causing human disease across the world, resulting in serious illness and mortality. Although antibiotic use in people is implicated as the primary driver, it is now widely acknowledged that the use of antibiotics in animals contributes to the global health burden of AMR.

This understanding is based on evidence supporting the steps in the causal pathway: (a) the emergence of resistant bacteria or genetic determinants resulting from the use of antibiotics in animals; (b) the subsequent transmission of resistant bacteria or genetic determinants from animals to humans and vice versa via direct contact, the food chain and the environment; (c) the colonisation of people by bacteria with resistance genes of animal-origin; and (d) clinical impact on human health due to bacteria with resistance genes of animal-origin. These clinical impacts include for example increased incidence and severity of bloodstream infections, treatment failures, prolonged duration of illness and mortality.

There is a small but growing evidence base of landmark reviews that link antibiotic use in animals to human disease, and these studies underline the public health imperative to ensure responsible use of antibiotics in all animals, with a focus on reducing use from currently high levels in certain regions, species and production systems. It is understood that in some countries, antibiotic use in livestock accounts for 70% of all medically important antibiotic use (O'Neill 2015). A global overview by the World Organisation for Animal Health, OIE, reports total usage (correcting for animal biomass in each region) ranging from 39 mg/kg in Africa to 237 mg/kg for Asia, Far East and Oceania.

There is evidence that the level of public health risk of AMR arising from antibiotic use is dependent on the drug-bacteria combination in question, which has resulted in a particular focus on reducing the use of the fluoroquinolones, 3rd and 4th generation cephalosporins, macrolides and colistin – named as the ‘highest priority critically important antibiotics’ by the World Health Organisation. However, there is also a need to view the challenge through an ecological lens, recognising that bacteria of different species can acquire a range of new resistance genes from the environmental ‘resistome’ that support their evolutionary success. It is therefore responsible to mitigate veterinary use of all antibiotics where possible to reduce selection pressure, whilst protecting animal health and welfare.

Solutions

Antimicrobial resistance is the quintessential One Welfare challenge, with human, animal, and environmental dimensions to the risk factors, impacts and solutions to the problem. Despite the challenges, there is an opportunity for veterinarians in this space to deploy all the tools available to help farmers select, breed, and manage animals in healthier systems, requiring fewer interventions.

Most members of the veterinary profession have a clear understanding of their role in One Welfare and the need to manage and mitigate antibiotic use, to protect animal and human health and welfare in the future. There are, however, several constraints to driving progress. These include paucity of consistent data surrounding usage patterns and indications; dependence on medical sales for revenue; so-called 'defensive prescribing'; and husbandry systems reliant on antibiotics.

The lack of harmonised data collection and reporting systems to establish baseline use and enable monitoring of progress is a significant problem. Some countries and sectors have developed effective data capture systems, but these differ in terms of the data they collect and metrics they use. Veterinary surgeons and businesses have a role in establishing robust data collection systems that enable them to track their own progress, and remain accountable to their clients and to the regulatory bodies that may request this. The RUMA Targets Task Force has been instrumental in supporting data collection and reporting in the UK, an example of an industry-driven initiative.

The challenge of dependence on antimicrobial sales is, in many countries, a real and significant one. There is an ongoing need to ensure that financial outcomes do not influence antibiotic prescribing behaviours, which may necessitate a shift in business models towards an emphasis on selling services and diagnostic testing before treatment. Some countries such as Denmark have gone further by prohibiting medicine sales by veterinarians, by decoupling medicine prescriptions and sales.

‘Defensive prescribing’ is defined in the human health field as a “physician’s deviation from what is considered to be good practice to prevent complaints from patients or their families” (Ortashi et al, 2014). There is also a perceived client expectation of receiving a product from a veterinarian, which can drive certain prescribing behaviours. Both of these social drivers can be addressed by better understanding client expectation, managing these expectations through education, effectively communicating with our client base and the public, having confidence in the inherent value of our veterinary services and advice, and charging appropriately for our time.

Some incidences of antibiotic use in animals are the result of management or husbandry practices that predispose to stress and disease. The FAO states that “in recent decades, the intensification of animal production due to the increasing demand for products of animal origin has led to an increasing overall use of antimicrobials” (FAO, n.d.). It is necessary for veterinarians to work with animal owners and keepers to reduce usage of antibiotics where possible and where necessary by not only ensuring judicious use when antibiotics are needed, but to critically evaluate husbandry methods and systems that may be predisposing to stress, disease, poor welfare outcomes, and ultimately antibiotic use in our patients.

"In recent decades, the intensification of animal production due to the increasing demand for products of animal origin has led to an increasing overall use of antimicrobials" - FAO

Veterinarians are amongst very few healthcare professionals that have the authority to prescribe antibiotics in many jurisdictions, which represents a considerable responsibility to ensure judicious use and minimise public health risk. Veterinary surgeons occupy an extraordinary niche at the human-animal-environment interface, and arguably of all professions, have the most acute theoretical and practical understanding of the importance of One Welfare. Antimicrobial resistance is the quintessential One Welfare challenge, with human, animal, and environmental dimensions to the risk factors, impacts and solutions to the problem. Despite the challenges, there is an opportunity for veterinarians in this space to deploy all the tools available to help farmers select, breed, and manage animals in healthier systems, requiring fewer interventions.

A framework for organising interventions

A number of frameworks have been adopted for antibiotic stewardship policies in the veterinary sector. However, the ‘3Rs’ framework – Reduce, Replace and Refine – has been used in recent years in the UK agriculture industry by RUMA, and numerous food businesses. The 3Rs was originally devised by Russell and Burch in 1959 for the purposes of reducing, replacing and refining the use of animals in research. Repurposing this framework has been useful to structure the necessary actions and behaviours around judicious medicine use in animals and can be a useful way for veterinary surgeons and veterinary businesses to structure their approaches and policies.

Here, the ‘3Rs’ goals of antibiotic stewardship, in animal agriculture are presented as an example:

1. REDUCE the annual usage of antibiotic agents in animal agriculture/aquaculture, per unit of livestock produced, whilst preserving animal health and welfare.

Example of implementation: Usage data should be monitored in terms of livestock species and antimicrobial classes. The routine use of prophylactic treatments should be discontinued. The use of medicines classified by WHO as ‘highest priority critically important’ to human health should not be used unless supported by diagnostic test results.

2. REPLACE the use of antibiotic agents in animal agriculture/aquaculture where possible, with sustainable solutions to prevent diseases such as vaccination and improved husbandry practices, to protect animal health and welfare.

Example of implementation: Proactive herd/flock health planning and analysis of medicine records should support the identification and control of prevalent diseases on farm, with a view to replacing antibiotic use with sustainable alternatives such as vaccines, biosecurity policies, improved husbandry practices and application of novel technologies.

3. REFINE the use of antibiotic agents in animal agriculture/aquaculture, by ensuring the responsible and informed selection and administration of products to animals that have a clinical indication for treatment.

Example of implementation: Responsible medicine dispensation and communication on correct medicine use (including handling, storage and disposal) by vets to farmers, for animals that have a therapeutic or metaphylactic need for treatment. Support the appropriate use of diagnostic testing, and the training of farm staff involved in animal care on responsible medicine use.

The replacement of antimicrobials with more sustainable alternatives that address the root causes of animal health challenges have been quite successful in some countries. For example, in some European countries where antibiotic use for growth promotion has been banned for decades, measures to mitigate use have included reduced stocking rates, better management and improved biosecurity. Many of these interventions have collateral sustainability benefits in other areas, such as animal welfare.

References

O'Neill, J. Tackling drug-resistant infections globally: Final report and recommendations. The Review of Antimicrobial Resistance Chaired by Jim O'Neill. Available from: https://amr-review.org/sites/d... [Accessed 9 Feb 2022] (2016)

O'Neill, J. Antimicrobials in agriculture and the environment: Reducing unnecessary use and waste. The Review of Antimicrobial Resistance Chaired by Jim O'Neill. Available from: https://amr-review.org/sites/d... [Accessed 9 Feb 2022] (2015)

Ortashi, O., Virdee, J., Hassan, R. et al. The practice of defensive medicine among hospital doctors in the United Kingdom. BMC Med Ethics14, 42 (2013). https://doi.org/10.1186/1472-6...

Food and Agriculture Organisation (no date). Antimicrobial Resistance. https://www.fao.org/antimicrob...

Van Boeckel, T. P. et al. Reducing antimicrobial use in food animals. Science (80-. ).357, 1350–1352 (2017).

Engberg, J., Aarestrup, F., Taylor, D., Gerner-Smidt, P. & Nachamkin, I. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates. Emerg. Infect. Dis.7, 24–34 (2001).

Van Boeckel, T. P. et al. Global trends in antimicrobial use in food animals. Proc. Natl. Acad. Sci.112, 5649–5654 (2015).

Ritchie, H. Antibiotic use in livestock in Europe, 2011 to 2016. Our World in Datahttps://ourworldindata.org/gra... (2017).