Antimicrobial resistance (AMR) is one of the most serious and urgent public health challenges of our time and its impact on our ability to use antibiotics has the potential to reverse many of the gains of modern medicine. As part of World Antimicrobial Awareness Week 2022, the Ineos Oxford Institute for Antimicrobial Research and Oxford Martin School hosted a one day symposium: The rising tide of antimicrobial resistance – a high price to pay. This brought together leading experts from research, industry, policy and financial sectors to discuss the threat of AMR and new opportunities to tackle it.
The need for an integrated approach
Around 1.27 million people are already thought to die every year as a direct result of drug resistant infections, with this burden rising rapidly worldwide. But widespread resistance to antibiotics would have much wider health impacts, effectively putting an end to safe organ transplants and surgical procedures and making every cut or scrape a potential gateway to a deadly infection. Furthermore, as explained by Professor Hanan Balkhy - the first Assistant Director of AMR at the World Health Organization – at the symposium, AMR is far more than a human health issue, being intrinsically linked with animal and environmental health – particularly as around 70% of antibiotics are used in livestock production. Since AMR has multiple drivers, she argues, it needs to be tackled on multiple fronts, with all stakeholders and sectors working together effectively.
This has helped catalyse a movement away from tackling these issues in isolation, to instead adopt a coordinated ‘One Health’ approach that recognises the interconnections between people, animals, plants and their shared environment. Achieving this at the level of individual countries, however, requires tailored national action plans that reflect local countries. She made the point that in low income countries, for instance, many people currently die because they are unable to access antibiotics at all.
Nevertheless, even with strong national leadership, action plans are unlikely to be effective unless civil societies are engaged. According to Professor Otto Cars, founder and senior strategic advisor at ReAct, local communities need to be empowered to understand the situation in language they readily understand. One challenge, he said, was that unlike HIV/AIDs or cancer, AMR is not itself a disease. This creates a need for evidence-based narratives on how AMR ultimately impacts areas such as food justice, poverty reduction, the environment and universal health coverage.
The power of big data
Besides narrative and understanding, robust data is also key to advocate for policies and action, as Dr Janet Midega, Senior Research Advisor at the Wellcome Trust explained. She described the work of the Global Research on Antimicrobial Resistance (GRAM) Project to address a critical lack of reliable information on the worldwide extent of AMR. This four-year project, a partnership between the University of Oxford and the Institute for Health Metrics and Evaluation (IHME) at the University of Washington and hosted at the University of Oxford’s Big Data Institute, brought together surveillance data from 204 countries to generate the first comprehensive estimate of the global burden of AMR, for 88 different pathogen-drug combinations. This landmark study, published in The Lancet in January 2022, found that an estimated 4·95 million deaths were directly or indirectly associated with bacterial AMR. Low income countries were disproportionately affected, particularly Sub-Saharan Africa which saw at least 255,000 deaths from resistance in one year. But even this ground-breaking work was limited by a lack of good quality data in many regions. Future work, Dr Midega said, should focus on building capacity in low and middle income countries to capture data that links diagnostics with patient outcomes.
The view from the ward
Professor Neil Mortensen, President of the Royal College of Surgeons of England, provided the perspective from the hospital operating theatre. He described the situation before antibiotics when entire hospital teams would be dedicated to cleaning and dressing wounds in an attempt to minimise potentially deadly surgical infections. There was no doubt that prophylactic use of antibiotics during operations saved lives, but injudicious use could have far greater long-term repercussions. With the sheer volume of procedures carried out (for instance, over 90,000 knee replacements in England each year), even a small increase in surgical infections would translate into thousands of affected patients. He called for a culture change within clinical teams, alongside greater research into antibiotic-free alternatives to infection control, such as vacuum-mediated wound closure and even robotic-assisted surgery.
Arlene Brailey, Patient Support Lead at Antibiotic Research UK, concluded the first session by sharing powerful stories from patients who have been affected by drug-resistant infections and describing the real-life impacts on their economic situation, and physical and mental health.
Turning antibiotics from ‘market failure’ to an attractive investment
The second session focused on the economic challenges to tackling AMR, and how to address the current ‘market failure’ to develop new antibiotics and alternatives. Dr Laurence Roope, from the University of Oxford’s Health Economics Research Centre, explained that a significant economic barrier for drug companies was the low profit margins that infectious diseases represent, compared with non-communicable illnesses. As soon as any new antibiotic is developed, there is immediate pressure to restrict its use to avoid selecting for resistant bacteria, which restricts the return a company can make through the current patent system. Instead, he proposed a ‘Netflix-like’ subscription model, already being trialled in the UK. In this model, individual countries contribute to a global health impact fund which pays drug companies a lump sum for developing a new antibiotics based on the net health benefit.
How to incentivise antibiotic research and development was a theme also discussed by the Lord Jim O’Neil of Gatley, who chaired “The Review on Antimicrobial Resistance” commissioned in 2014 by the UK Government. He argued that the COVID-19 pandemic had demonstrated that pharmaceutical giants could rapidly pivot to apply their capabilities to new areas when provided with immediate government funding. However, consumers also had a major influence in tackling AMR he said, citing the example of fast-food outlets committing to remove antibiotics from their supply chains to protect their corporate image.
Making an economic case for government action
According to Dr Julie Robotham of the UK Health Security Agency, one strategy to encourage governments to channel money towards tackling AMR is to present an irrefutable economic case that quantifies the monetary cost of inaction. But with AMR encompassing many different pathogens and drugs, and affecting countries to different extents, this remains extremely challenging. Ultimately, Dr Robotham said, what is needed is a user-friendly database with unit costs of AMR for different pathogen-drug combinations and settings.
Dr Catriona Waddington of the Fleming Fund (a UK aid programme) spoke of the particular difficulties of making a case for AMR investment in low income countries, especially for surveillance programmes. Ideally, she said, AMR surveillance would be seen as a global public good and form part of government budgets. But the average cost of an AMR surveillance programme in a low-income country costs around £2.5 million per year: equivalent to the government health expenditure for 78,000 people. Another key issue is that patients in these countries typically have to pay for healthcare costs out of their own pocket, making it extremely unlikely that they will have a diagnostic test for an infection. A critical first step, Dr Waddington said, was ensuring that diagnostics are not more expensive than antibiotics themselves.
Responsible investment – an untapped opportunity?
But there could be a significant source of – as yet untapped – investment for tackling AMR, according to Anita McBain of Citi Research. She spoke of the exponential rise of responsible investment, driven by increased scrutiny over whether funds are applied towards societal benefit. Over the past five years, she said, AMR had moved from a frontier theme in responsible investment to an attractive candidate for those seeking to develop new investment solutions that prioritise human health and wellbeing, human security, and social inequality. But leveraging this will require closer working and clearer communication between AMR researchers, NGOs, industrial partners and investors. As she put it, ‘scientists rarely write for investors.’
Responsible investment, social responsibility and public awareness were some of the reasons credited by Sir Jim Ratcliffe, Chairman of INEOS, for becoming interested in AMR and launching the Ineos Oxford Institute for Antimicrobial Research in 2021. The goal, he says, is to combine the expertise of multiple stakeholders, including industry and academia, to address this problem. ‘Can you imagine, in 20 or 30 years’ time, if we don’t have a cupboard full of antibiotics that we can rely upon? It’s unimaginable. We need to find new antibiotics, that’s really what this is all about.’