Antimicrobial resistance (AMR), the natural development of resistance to therapies by infectious organisms, is a slow growing pandemic. This ‘silent’ pandemic is happening now, globally, and is on the rise, compounded both by human behaviours and lack of investment. AMR is complex, respects no borders and generally disproportionately impacts low-and middle-income countries (LMICs). Human Health, our food chain, biodiversity and the very sustainability of our planet depends on our working together to mitigate AMR.
It is clear that no health system can function properly without effective treatments, including antibiotics. They and other anti-infectives are essential infrastructure in health systems and the food chain. The right treatment at the right dose and right time can be curative but, the wrong treatment, too low or high a dose, or event bad timing can drive the development of genetic mutations- causing resistance to the treatment. This is true for tuberculosis, malaria, HIV, bacteria, fungi and all infectious organisms.
Resistant organisms are often called ‘superbugs’ because they proliferate in the presence of standard treatments. But there is worse: not only can superbugs pass the resistant genes onto their own progeny but, for instance, bacteria can also pass the resistance genes to unrelated bacterial species. We vertebrates live with many bacterial and viral species in our guts, on skin and in orifices. This is collectively known as the microbiome. Resistant organisms can hide in the microbiome until activated either by a breach of skin or host loss of immunity, and they can also be passed to other vertebrates and cause infection.
Box 1: Drivers of AMR
Resistant infections are a key issue for global health because they directly increase human suffering and cause otherwise preventable deaths. Similarly, we see impacts on the food chain, with animals, fish and crops unnecessarily dying from preventable infections. Meanwhile, drugs that fight infections, such as antibiotics, cause environmental pollution, particularly of rivers and oceans. The chemical entities (or their precursors and breakdown products) from antibiotic manufacturing and excreta from animals and humans, mean that the environment spreads AMR, but also that AMR negatively impacts biodiversity. So AMR adversely impacts every part of and, inhabitant of our planet. It is for this reason that AMR is known as a ‘One Health’ problem.
The challenges posed by AMR are actually very similar to those posed by global warming. AMR is already damaging the global economy and this lowering of GDP will only amplify, and intensify socio-economic inequalities, unless we find and put into practice solutions. Clearly, no one country, not even one region, can solve the problem of AMR on their own. It is only by collaboration, harnessing affordable innovation and working across sectors that we can ensure the sustainability of our food chain – indeed, the survival of our race.
The solutions seem relatively simple and sensible. After all, we need better infection prevention and control (IPC) to reduce the risks posed by the spread of diseases, as has been exposed and exacerbated by the spread of COVID-19. This requires clean water and sanitation, and includes hygiene and disinfection, such as hand washing. Proper air handling and effective vaccination programs, alongside proper access to and appropriate use of high quality anti-infectives, are also important measures to prevent infections from spreading. We need stronger health systems for humans and animals and resilient food chains. We need responsible use of antimicrobials - ‘stewardship’ – which in turn demands better diagnostics and vaccines to respectively detect and prevent infections. And, of course, we need new treatments to replace ineffective or inaccessible ones.
All these problems and systemic needs have all been laid out clearly during the pandemic of COVID-19. So is our problem with AMR a lack of understanding? Has AMR been creeping up on us so slowly the politicians have not taken notice, aggravated by short political electoral cycles and the paucity of data showing the economic impact of AMR? Or is it that those of us who really understand the problem have failed to make our voice heard, even that we have not found the right words to convey our messages?
There is excellent work happening across the world, but sectors, countries and even communities are operating in silos. We argue that if we just share, scale-up and make sustainable what some countries or groups are doing or planning (for examples see Box 2) that we could make a big impact immediately. However, to really address AMR and save modern medicine for future generations, we are going to need even more global coordination.
Box 2: Global good practice
AMR is complex, but it is possible to group the actions needed across ‘systems’, while still recognising the interactions between all systems and the essential need for collaboration across sectors. This can prove difficult at the national level and yet, like Climate Change, we need to collaborate globally to really mitigate the impact of AMR on future generations, in an increasingly connected world.
In the human health system, we must ensure fair and equitable access to anti-infectives for people wherever they are and whatever their economic status. Alongside this, we need effective capacity and awareness building, surveillance and diagnostics to drive good stewardship. The public need to understand the present limitations of our armamentarium- especially that antibiotics only work for the right bacteria and never work to treat viruses and the common cold. Regulations and clinical guidelines for prescribing, dispensing and use are helpful.
Since the 1980s, we have not brought into routine clinical practice any new classes of antibiotics. While the scientific research to find and develop new antibiotics is hard, the real problem is a classic economic problem of ‘market failure’. Society has grown used to paying very little for antibiotics, so it is judged not to be in the interests of pharmaceutical companies’ profit and thus shareholders to research and develop new antibiotics and anti-infectives. The ever-rising rate of multi drug resistant and extreme drug resistant TB across the world is a testimony to this, as is the rise of malaria resistance to treatment and increasing bacterial resistance to antibiotics across the world - particularly in LMICs.
We have to collaborate across the world to bring new treatments to markets and patients everywhere. This means that we have to value new antibiotics and new anti-infectives not by the classic health economic measures of quality life years and life years saved, which are standard Health Technology Assessment criteria- but actually by looking at the value these new antibiotics and treatments give to society as a whole. We also need to protect the efficacy and availability of any new treatments by separating the volume sold (a driver for resistance to develop) from what Society pays for them. This is called ‘delinkage’ and if countries collaborate, we can really invigorate the R&D pipeline. Together, countries need to work to prevent ‘free riders’ from high income countries, while simultaneously ensuring access for LMIC patients. Research, development, stewardship and access are all interlinked.
Box 3: The UK’s ‘Netflix’ subscription model pilot
Just as human behaviours and interventions can impact global health security, we must also make changes that benefit our global biosecurity. As the global population rises, there is a greater demand for protein; meanwhile, development drives demand for increased quality and variety of foods, including fast foods. This need has been driving intensification of farming across the world. Infections in animals become more common with crowding and animal transport. Farmers meanwhile, seek to maximise protein production and profits which has led to the abuse of antibiotics. They are used not just to treat infections but also to prevent infections (prophylaxis), even of whole flocks and herds (metaphylaxis) and for growth promotion. After all, routine treatment is cheaper than biosecurity! This approach is short-term and risks the sustainability of our food system in the future.
We must collaborate to have a global agreement on ways for stopping antibiotic use for growth promotion and metaphylaxis, and phasing out prophylactic use. Meanwhile, agreement should be reached urgently to end the use of highest priority, critically important human antibiotic and anti-infective agents on animals. We need cheaper easier ways of delivering biosecurity, sustainable food systems and safe uncontaminated environments promoting biodiversity. The world needs innovation to deliver affordable vaccines and different methods for growth promotion.
The fastest growing sector for protein production for human consumption is fish farming, which across the world is again very antibiotic and anti-infective dependent- such that generally the treatments are tipped into the water where the fish are being raised alongside, or mixed in with the feed. Fortunately, this is not the case for Norwegian and Scottish farmed salmon and trout. They use a cocktail of vaccines, which can now be dispensed by robot, into each fish at an early stage of development - thus successfully reducing antibiotic use and water contamination. Such an approach could be developed for all fish farming. Another approach would be to breed or engineer infection resistant fish and crustaceans for farming.
Box 4: Graph of antibiotics used in Norwegian farming of trout and salmon (The Norwegian Medicinal Depot, The Directorate of Fisheries)
Trees and crops in some countries, are also inappropriately treated with antibiotics and anti-infectives. From streptomycin spraying of citrus trees in Florida and California, to the injection of citrus trees with antibiotics in Southeast Asia, and crop spraying in fields, there is insufficient attention paid to the short and long-term consequences on human and animal health- let alone the run-off into the environment and water-systems of our world. Again, we need to use modern breading techniques or engineering to develop infection resistant plants and secure our food systems of the future – especially for economies and communities whose livelihoods depend on healthy, productive workers and healthy, sustainable food systems.
Antibiotics and their precursor chemicals are resistant to being broken down so that animals, including humans, excrete (through urine and faeces) more than 70% of any treatment used. Only the most modern sewage treatments remove these pharmaceuticals before returning water to rivers, the water table and seas. Particularly high levels are found in run-off from hospitals and high use intensive farming. Meanwhile most antibiotic factories are old and put out effluent with uncontrolled levels of Active Pharmaceutical Ingredients (APIs) and antibiotics. This pollutes waterways as drinking sources and habitats - perpetuating both biodiversity loss and health effects, as well as transmitting resistance. We need to collaborate together as nations to agree and implement safe levels of antibiotics, APIs, residues, resistant pathogens and genes in our whole environment including water systems.
Box 5: Examples of water contamination
We have watched COVID-19 work its way across the world and how different nations have handled this, with shared learning through inter-governmental fora and multilateral organisations alongside the scientific and general press. The speedy sharing of genomic data - led in January 2020 by China - is an example of how transparency and collaboration makes a tangible difference to human lives and our economies and how science and innovation can save lives. We must build on this.
Box 6: Learning from COVID-19 to tackle AMR
There is already some good collaboration aimed at mitigating AMR. This is at the level of the UN family, where the work on Human health systems is led by the World Health Organisation (WHO), and on animal and agriculture health systems led by the Food and Agriculture organisation (FAO) with the World Organisation for Animal Health (OIE). These three organisations Collaborate on AMR as the ‘Tripartite’ and now, with greater involvement from the UN Environment Program (UNEP) and the development of effective ‘quadripartite’ co-working in order to fully capture all the One Health impacts and solutions of AMR. These all support the new United Nations Group: the Global Leaders Group for AMR, whose purpose is advocacy to raise AMR up the political agenda, and increase momentum for collaboration and solution finding.
But AMR is even bigger than these four organisations. It is a development issue and an economic issue putting the delivery of the sustainable development goals (SDGS) very much at risk if we do not take effective action now. Countries need to come together to collaborate and work across the UN system to drive urgent action. We need to work holistically recognising this is not just a human health matter but it involves animals, crops, water, biodiversity and sustainability.
Early wins include banning the use of medically important antibiotics in the food chain, introducing environmental standards for discharge whether from manufacturing, high use hospitals and farms or sewage more generally, and valuing innovation including vaccines, diagnostics and new treatments appropriately. We need to strengthen infection prevention and control for humans, animals and fish farming alongside regulation of manufacturing, quality and use of anti-microbials across all sectors. And we need good one health surveillance across the world to ensure we fully understand the present and developing burden of antimicrobial resistance.
AMR needs to be embedded in all agendas whether discussions on COVID-19 and Health Security, the Sustainable Development Goals, the UN Food Systems Summit or discussions on water and oceans across our planet and more. AMR has to be at the centre of any negotiations about preparedness and response to pandemics including sitting at the heart of any future ‘Pandemic Global Treaty’ for the world.
There is a role for everyone in mitigating AMR- led by governments supported by the public and involving innovative industries. We had to start by having our One Health National Action plans for AMR and then funding and implementing them. Now, we need to collaborate to minimise the cross-border and global issues contributing to AMR. Nowhere can this be more important than through the development of a global treaty to mitigate AMR. This can either be a specific collaborative standalone treaty. Or, perhaps easier, we can as nations together ensure that AMR, as a slow pandemic is included in the treaty for pandemics as recently proposed by more than twenty world leaders.
Professor Dame Sally Davies is UK Special Envoy on Antimicrobial Resistance. Before this, she was Chief Medical Officer (CMO) for England and Chief Medical Adviser to the UK government from March 2011 to September 2019, having held the post on an interim basis since June 2010.
Dame Sally advocates globally on AMR. She has spoken on AMR at numerous events including the World Health Assembly side events, the G8 science ministers’ meeting in 2015, the Global Health Security Initiative in 2015, and the UN General Assembly side event in 2016. She was chair of the 2013 AMR forum at the World Innovation Summit for Health (WISH) and was for three years the chair of the WHO Strategic and Technical Advisory Group on AMR. Most recently, Dame Sally has been appointed a co-convener of the UN Inter-Agency Co-ordination Group on AMR, set up in response to the AMR declaration made at UNGA 2016.
Dame Sally was a member of the World Health Organization (WHO) Executive Board 2014-2016 and has led delegations to a range of WHO summits and forums since 2004.