An Evolutionary Arms Race

Around 700,000 lives are lost worldwide due to antimicrobial-resistant infections every year. Without viable antibiotic treatment options we may return to a dark age of medicine – a time when common infections or injuries could kill, and common surgeries and immunosuppressive therapies may become unfeasible.

Here we present the case for a collaborative One Health approach to antimicrobial resistance, recognising the contribution of human medicine and animal agriculture to both the cause and solution. We propose that food companies ‘replace, reduce and refine’ the use of antimicrobials as a sustainable approach to phasing out the unnecessary and irresponsible use of antibiotics in animals.

Bacteria are not respectful of boundaries. Ubiquitous in all settings, they are able to move between human populations, animals and the environment, as well as across national boundaries. For several decades we have been using antibiotics to control diseases caused by them. However, Alexander Fleming, discoverer of penicillin, predicted the inevitability of resistance arising as early as the 1940s in his Nobel Lecture due to their ability to mutate and exchange genes.

Every time an antibiotic is used, a selection pressure is exerted on a bacterial population, allowing only the resistant bacteria to survive. In fact, some bacteria will already contain genetic material conferring resistance to an antibiotic, even before it is exposed to an antimicrobial agent. For these reasons, we now find ourselves in an evolutionary arms race with bacteria, and without rapid and drastic changes to the way antibiotics are used, in humans and in animals, we are set to lose.

On 21st September 2016, the UN held a high-level meeting on antimicrobial resistance at the UN headquarters in New York. The resulting declaration to combat proliferation of antibiotic resistance signed by all UN Member States marked the beginning of a concerted global effort to meet the UN’s Sustainable Development Goals through improved antimicrobial use. This is a welcome step as no new classes of antibiotics have been developed in the last 30 years, resulting in fewer and fewer treatment options.

The inevitability of resistance, alongside poor returns from short-term therapies like antibiotics, make research into developing new antibiotics an unappealing investment for big pharmaceutical companies and their shareholders. While new classes of antibiotics and medical alternatives are urgently required, the One Health approach helps us identify a series of integrated efforts aimed at improving the stewardship of these critical agents in our armoury for human health and wellbeing. By coming together as one health community – comprising doctors and veterinarians, farmers and scientists, economists and policy makers – we are best able to attain optimal and sustainable health for people, animals and the environment.

Growing antibiotic resistance

Agriculture represents a source of valuable protein for our growing global population, but also a source of zoonotic diseases, particularly food-borne infections. Use of antibiotics in food animal species has selected for antimicrobial resistant bacteria, and these represent a threat to human health. Several studies have made the link between antibiotic use in animals and antibiotic resistance in bacteria isolated from them, food products, humans and the surrounding environment. In particular, sub-therapeutic doses of antibiotics in animal feed and water as growth promoters select strongly for resistance.

In many parts of the world, agriculture is shifting from smaller family farms to larger, specialised intensive-rearing systems. With this comes associated risks and often a resultant increase in routine use of antibiotics to prevent disease and allow for increased stocking densities and improved feed efficiency. In the USA it is estimated that agriculture accounts for 80% of total antibiotic use, and of this 50% is for non-therapeutic use¹. The impact of rising levels of antimicrobial resistance will therefore not only be felt within human medicine but also in our food chain. With the recognised risk of antimicrobial resistant bacteria emerging in livestock and the environment, farmers, veterinarians and food companies must lead the collaborative action necessary to drive responsible use of medicines all along the food supply chain.

In response to emerging resistance some food companies have adopted policies focused on ‘no antibiotics administered never ever.’ Without systemic change of the agricultural system aimed at decreasing the underlying dependence on antibiotic therapy and prophylaxis this approach becomes unsustainable, and could represent an animal welfare issue. To achieve meaningful change in the way antimicrobials are used in agriculture we propose that food companies adopt the ‘3Rs’ framework. This framework promotes practical and evidence-based solutions to ‘Replace, Reduce and Refine’ the use of antimicrobials, and is sufficiently flexible to allow tailored stewardship programmes to be developed for individual species, production systems and farms across the world.

Replace, reduce and refine

The most effective way to replace antibiotic use is to eliminate the need for them, primarily through comprehensive disease prevention. This will require behavioural and attitudinal changes in both the farming and the veterinary profession where it has become habitual to utilise antibiotics as the first line of attack. In Sweden, a ban in antibiotic growth promoters was accompanied by housing improvements, partitioning, better hygiene, and ‘all-in, all-out’ practices. These measures decreased antibiotic use by 50% initially, with further decreases thereafter².

Secondly, efforts should be made to reduce the overall use of antibiotics in animal agriculture without compromising health and welfare. A first step would be to establish a consistent means for veterinarians and farmers to record and report their actual usage around the world. To realise the benefits of the One Health approach, this information should be shared widely to inform production practice, as well as antibiotic use and monitoring across all sectors including human health, animal health, crop use and aquaculture. In 2009 the Netherlands mandated a 50% reduction in antibiotic use within three years and implemented a data collection system to monitor antibiotic use involving veterinarians, academia and industry³. By optimising livestock living conditions they reduced use by 56% without compromising production or profit.

Thirdly, where antibiotics are needed to treat animals, effort should be made to refine their use to ensure they are as effective as possible. In conjunction with effective diagnostic tests, this means administering the right medicine at the correct dosage, for the right duration and using appropriate equipment. Appropriate labelling of drugs in terms of their importance to human and animal medicine may also aid in the responsible selection of products.

Finally, not all antimicrobials are created equal. The World Health Organisation classifies certain classes of antibiotics as ‘critically important’ to human health. In the this category of antimicrobials are the 3rd and 4th generation cephalosporins, fluoroquinolones, macrolides, glycopeptides and polymyxins (e.g. colistin)⁴. Furthermore, the World Organisation for Animal Health (OIE) published a list of antibiotics deemed critically important for treating serious animal diseases, and for which no or few other alternative medicines exist⁵. Unfortunately, four antibiotic classes are considered ‘critical’ to both human and animal medicine.

The 3Rs framework is our best opportunity to deliver the global One Health goal of safeguarding these vital medicines for future generations, whilst upholding our responsibility for the health and welfare of livestock, which are increasingly in demand to feed the planet’s growing population. Therefore, we propose that producers and food businesses take a progressive approach in banning the use of “highest priority critically important” antibiotics in animal agriculture. This will require supportive policies to phase-out their use over time, alongside measures to replace their use with sustainable alternatives and improved health practices. Such an approach will protect animal health, welfare and productivity, farmer livelihoods and our collective wellbeing.

Breaking our reliance on antibiotics

Like climate change, antimicrobial resistance requires global collaboration and universal solutions that can be adapted to different settings. Food production reform should ultimately benefit all – the producer, the consumer and the animals – which will require engagement of those in the food-producing industry, as well as the wider public. With a global population set to reach 9.7 billion by 2050 and corresponding food consumption to increase by more than 50%, new and innovative production methods are required⁶. Antibiotics are vital to maintaining human health, animal welfare, a secure food supply and a strong agricultural economy. However, this ‘miracle drug’ of the 20th century should not be used as a substitute for good animal husbandry practices.

Current industry reliance on antibiotics as a production tool is not sustainable and is leading to serious health risks for both animals and humans. To get us on the right path, a necessary first step is to implement comprehensive surveillance of antibiotic use and emerging resistance. This will help us to assess risk and provide early warning systems for new trends. Secondly, we must demonstrate that optimising management practices that break agriculture’s dependence on antibiotics is both a positive economic strategy for farmers and advantageous for public health.