Drug resistant infections: causes, consequences and considerations
We are honoured to be able to publish in full the transcript of Professor Dame Sally Davies keynote address at RSTMH's 2021 Annual Meeting.
Good morning. Thank you to the Royal Society of Tropical Medicine and Hygiene for hosting this Annual Meeting. By bringing together your Members and supporters from right across the world, you are showing just how important collaboration is in preventing, mitigating and responding to AMR. Science and policy matter globally. We know that for a One Health issue of the scale and complexity of AMR, no nation is an island; global health challenges may evolve, but the need for global collaboration, with RSTMH's community at the heart, continues.
I am speaking to you today as the UK's Special Envoy on Antimicrobial Resistance. Over the past two years in this role, I have continued to champion the need for action on AMR. By working bilaterally and multilaterally, publicly and privately, I act on behalf of the UK government to help the world move the mountains that it needs to in order to tackle the silent pandemic of AMR. I work with the countries from across the world, multilateral groups like the G7 and G20, UN organisations, Global Leaders Group on AMR, and private sector to compel action.
Exciting time for global health
This is an exciting time for global health. Over the past year, pace of innovation for COVID-19 vaccines has been unprecedented. The UK vaccine community was able to respond rapidly to COVID-19, thanks to UK Aid funding to the Oxford Group to develop the ChAdOx1 vaccine for MERS, since 2016. This enabled them to pivot when COVID-19 did emerge. And just this week, the World Health Organization have approved the breakthrough vaccine for malaria to be rolled out to children across sub-Saharan Africa.
Yet, at the same time, we face a crossroads and a reckoning for AMR. The WHO have gone so far as to say that "the world is failing on AMR" because of the lack of treatments in development that will fill critical public health needs. This is a sober reflection of the stark reality we face. If we are to learn our lessons from COVID-19, then we need to make bold moves – now.
We all have a stake in controlling, preventing and treating infections. Already, some pathogens, such as Neisseria gonorrhoeae, have evolved strains that can no longer be treated successfully with any licensed antibiotic. For patients with HIV, 90% of whom receive antiretroviral therapy, 80% have resistance to two or more of their drugs – these people are 70% more likely to die within two months of being admitted to hospital than those without drug resistance.
COVID-19 has exacerbated AMR
Emerging evidence suggests that COVID-19 has exacerbated AMR, due to a groundswell of increased antibiotic consumption. Around 75% of COVID-19 patients receive antibiotics, despite only 3.5% and 14.3% of patients hospitalised respectively for bacterial co-infection and secondary infection. We may well see a scenario where one pandemic accelerates another if we don't work to preserve these precious resources.
In 2019, the IACG warned that there was "no time to wait". The two years that have unfolded and unleashed devastation on the world since – through COVID-19, but also through climate emergencies, mean that there is now neither time nor excuses left for us to act. We must not forget that, for many, it is already too late – they have died.
Across the UN community, we are resolved not to allow the crippling inequity caused by COVID-19 define our future too. I am proud of the work that the Global Leaders Group on AMR is doing to position AMR at the top of the global political agenda. Comprising global Heads of State, ministers, scientists, and representatives of the private sector and civil society, this Group is catalysing political action on AMR. I am honoured to be a Member of this Group, and advocating for our top priority areas: political action, transforming systems to use antimicrobials sustainably, improved surveillance, funding National Action Plans, increasing innovation, and better understanding environmental pathways to AMR.
Antibiotics are critical infrastructure
This year, multilateral actors have moved on AMR – we need more data and collaboration to turn these steps into strides. Earlier this year, I participated in the United Nations’ High-Level Interactive Dialogue on AMR, which was a milestone to assess global progress to date and commit to actions going forward. Leaders from across the UN, governments and private sector joined, and the President of the United Nations General Assembly warned that ignoring AMR would be at our peril, and urged all Member States to strengthen global governance and engagement on AMR. Over 110 Member States signed the resulting Call to Action document, which commits to aligning AMR with other important global agendas, including pandemic preparedness and climate change.
Momentum is here, and growing. In June, the Leaders of the G7 committed to "act now" to strengthen our global health security systems to bolster our preparedness to tackle AMR – giving an unequivocal mandate for action from all sectors, addressing a range of drivers of AMR.
Antibiotics are critical infrastructure, which our healthcare systems depend on to be effective. Yet, most countries under-value and under-invest in treatments, diagnostics and vaccines, as well as sanitary interventions and surveillance. This means that we lack the innovative novel treatments we need. Of the 26 antibiotics in clinical development that are active against the WHO priority pathogens, only two are active against the critical multidrug-resistant Gram-negative bacteria. This trajectory is a problem for all of us.
Broken antibiotic market
As it stands, the cost of developing, registering and marketing antibiotics is high, but pricing has seen a race to the bottom – leaving us with a broken antibiotic market. Pharmaceutical companies have few incentives to invest in antibiotics, seeing a net loss of $100m from 2014 to 2016. So for the 75% of late-stage antibiotics in the R&D pipeline which are developed by SMEs, low returns risk survival. Out of the most recent eight new antibiotics to be registered, six were from small biotechs. Two of these went bankrupt, and another was forced to merge to survive. This means that innovative treatments never make it to wards or patients to be used.
To address this fundamental economic problem, our G7 Finance Ministers have made commitments on AMR for the first time, showing that tackling AMR is integral to current and future health and economic prosperity. They will be working with Health Ministers to explore how we can ensure that new and novel antimicrobial treatments can be developed and accessible for the patients that need them. They’ll be working with industry too to make sure that innovation works for everyone, and reaches everyone. This is will need to be underpinned by data and evidence, now and in the future, on antimicrobial use and antimicrobial resistance to guide our innovation to target the most dangerous and priority pathogens and unmet national health needs.
We'll be driving forward progress that is already starting to be made across the G7 countries. In the UK, our innovative "Netflix model" is a world-first system to pay for antibiotics by subscription- based on their value to society, not on the volume of pills used. This approach benefits NHS patients by guaranteeing both sustainable use and sustainable supply of antibiotics– by embedding stewardship and by giving companies certainty of demand. Following a rigorous process with expert clinical input, two treatments, Cefiderocol (Fetcroja) manufactured by Shionogi, and ceftazidime with avibactam (Zavicefta) manufactured by Pfizer, have been selected to move to an innovative health technology evaluation process. We hope that these will be available to NHS patients by 2022.
Market needs to be attractive to investors
We can also look to the PASTEUR Act in the US, which has been reintroduced with bi-partisan support to Congress. This would establish a subscription mechanism by investing $11billion over ten years, based on the assessed value of drugs to patients. Crucially, this would ensure that patients covered by federal insurance programmes can access treatments at no cost, whilst guaranteeing revenue for the companies.
Stewardship forms an underpinning component of the Act – companies will be required to develop education and communications strategies on appropriate antimicrobial use, including for those with limited English proficiency or disabilities. The Act also provides financial support for hospital antibiotic stewardship programmes.
If the Act passes, it will send a signal to the world and take us mightily far in showing that the challenging market can be overcome. I am clear that collectively, the G7 countries can make a difference to making the antibiotic market far more attractive to investors.
AMR and G7
The G7 aren't stopping there. Our G7 Health Ministries have also agreed to work with industry to strengthen supply-chain resilience through a broader and more geographically diverse, quality-assured manufacturing base. At the moment, we know where our clothes and food come from, but not where our antibiotics come from. By mapping and strengthening antibiotic supply chains, we can get a grip of this – and, crucially, strengthen our fragile supply chains. As of June 29, 2020, 10.5% of all drug shortages listed by the US Food and Drug Administrations were antibiotic shortages. This must change.
I’m also delighted that the G7 will be working with the AMR Industry Alliance to accumulate knowledge of AMR in the environment. We know that waterways can be reservoirs of transmission, detrimentally to the health of humans, animals and our environment. But we need far more evidence of the contamination, mechanisms, causes and impacts of AMR emerging and spreading in the environment – and this will empower us to agree international methods to curtail it. In fact, sewage surveillance offers an economically affordable and scalable method of global AMR surveillance, and can give us insights into the prevalence and diversity of AMR genes between sites and countries.
Global scale of AMR not fully understood
This builds on a landmark new programme of pathogen surveillance across agriculture, food and the environment launched by the UK government this year. This system will pilot a national surveillance network, using the latest DNA-sequencing technology and environmental sampling to improve the detection and tracking of foodborne and antimicrobial resistant pathogens. This project will help us to understand the complex role that the environment plays in the development, maintenance and transport of resistance leading to the exposure of people, animals and crops. I am excited that the use of genomics will enable us to begin to add environmental knowledge to build a true One Health approach to AMR.
Currently, the global scale of AMR and Antimicrobial Use is not fully understood. We rely on geospatial mapping and proxies to give us an insight, but without a comprehensive picture, we are operating in the dark. This is where we look to programmes like the UK's Fleming Fund that work to strengthen surveillance systems across the world, investing in countries’ clinical microbiology capacity to carry out their own surveillance, including submitting data to GLASS.
The UK government’s Fleming Fund is the first major international aid investment dedicated to addressing AMR with data at its heart. Across 24 countries, we are bringing evidence and people together to support countries with laboratory equipment and skills.
Surveillance data is vital at global, national and local levels. For politicians and policy-makers, accessible data provides an understanding and ownership of the challenge. On the ground, data empowers healthcare workers with the tools they need to drive solutions that work for the context they are facing.
For example, in Bangladesh, we are piloting a mobile app which for vets in the field to optimise prescription practices for poultry. This will give farmers access to expert advice and the tools they need for diagnostics and treatment – and it can also be scaled up to more countries.
I am proud of the collaboration between the Fleming Fund and the International Vaccine Institute to create demand for AMR data. Teams on the ground have been digitising, collecting and assessing data in Timor-Leste, Papua New Guinea, Laos, Bhutan, Nepal and Bangladesh. Our joint project will identify gaps in data and areas for improvement in the future – this will be useful for the countries themselves, and for policy-makers globally.
One Health approach
The Fleming Fund is driven by a One Health approach that engages multiple ministries and sectors. We support the CommonWealth Partnerships for Antimicrobial Stewardship (CwPAMS) to develop guidelines and strategies to improve infection prevention control measures and build antimicrobial expertise. I am thrilled to see the progress CwPAMS have made since 2019 to leverage the expertise of NHS institutions, volunteers and technical experts to strengthen the capacity of the national health workforce and institutions in Ghana, Tanzania, Uganda, and Zambia in antimicrobial stewardship. CwPAMS have also supported local pharmacists in Zambia to produce their own hand sanitiser to help respond to COVID-19 in their communities.
It's not just governments who have to sit up and pay attention to AMR. Many investors now see antibiotic stewardship as a proxy for how well an animal protein company can manage pandemic risk. Many are not doing very well at this – over 70% of the world’s largest meat, fish, and dairy companies, worth a combined $338bn, ranked as high risk for antibiotic stewardship. It doesn't have to be this way. The private sector can take the lead in investing responsibly, including in supply chains that do not use antibiotics for growth promotion.
Last year, the UK government, in collaboration with FAIRR, the UN Principles for Responsible Investment, and the Access to Medicine Foundation launched the Investor Action on AMR initiative during the World Economic Forum in Davos. We are calling on investors to commit to making sustainable investments and align with global best practices on AMR by incorporating AMR into their ESG standards. To date, 14 investors from across the world with a collective asset portfolio of over $7 trillion have signed up.
Movement is gaining traction
This movement is gaining traction. McDonald's have pledged to reduce the use of antibiotics in its global beef supply by the end of this year. In the UK, six of the ten leading supermarket companies have now banned the routine use of antimicrobials in their food supply chains.
Consumers are putting their money where they want their mouths to be. There’s a great scorecard in the US that helps consumers understand the different company policies on antibiotic use. And in my role as Master of Trinity College, I am supporting my students to become AMR activists by tabling resolutions at AGMs to push for the elimination of antibiotics from supply chains.
I am clear that everyone has a role in AMR – though it is up to all of us to guide people to understand that role, and truly own their role. For politicians to own the issue, we need to be much better at quantifying the social and economic costs of AMR in the immediate term and the long-term. For frontline workers, whether farmers, vets or clinicians, we need to give them the tools to drive forward solutions that work in their own local contexts. For young people, we need creative ways of sharing messages, including through art and drama that make lasting impacts on their behaviours and activism, such as through The Mould that Changed the World musical.
I look to all of you here today to play a role and keep collaborating to galvanise innovation, access and stewardship in a way that means we are truly building forward from COVID-19, equitably across the whole world. Our global leaders are acting, and we need everyone to act as leaders in their own communities or sectors to accelerate the momentum – and learn the COVID-19 lesson once – and once only. Thank you.