Stepping up to the plate on antimicrobial resistance

IFPMAEduardo Pisani, Director General of IFPMA – the International Federation of Pharmaceutical Manufacturers and Associations.

Antibiotics have made modern medicine possible. Before the discovery of penicillin in 1928 and the recognition of its therapeutic potential, there were few tools doctors could use when patients came to them with common or minor infections from simple paper cuts. Today, complex medical interventions are made possible by the use of antibiotics.

However, seventy years on, the rise of antimicrobial resistance (AMR) is threatening the effectiveness of these tools. A hallmark of antibiotics is that they lose their effectiveness over time as bacteria naturally evolve and mutate and so become resistant to the medicine’s power.  Estimates from the UK Review Team on AMR predict that the death toll from drug-resistant infections could rise from 700,000 today to 10 million by 2050, and that the burden put on healthcare systems would amount to trillions of dollars.

These statistics and scale of the challenge of tackling antimicrobial resistance may seem daunting, but they have certainly galvanised action. In many ways, the global pharmaceutical industry is already at the forefront of leading action to address antimicrobial resistance.

In January this year, a major milestone in the global response to AMR was achieved, when over 100 companies and 13 associations signed the Declaration by the Pharmaceutical, Biotechnology and Diagnostics Industries on Combating Antimicrobial Resistance. The Industry Declaration set out three key commitments. First, to reduce the development of drug resistance; second, to increase investment in R&D to meet global public health needs; and third, to improve access to high-quality antibiotics and vaccines for all. The industry also called on governments to commit to allocating the funds needed to create a sustainable and predictable market for these technologies while also implementing the measures needed to safeguard the effectiveness of antibiotics. There is a clear need for global coordination of stewardship, conservation, hygiene, and the creation and use of new commercial and incentive models for antibiotics, vaccines and diagnostics, to be delivered through local action.

The Declaration is a living document, and to keep up the pace with the evolving landscape of scientific breakthroughs and policy action, it will be updated every two years. Alexander Fleming himself is said to have called the discovery of penicillin “a triumph of accident”. Since, we’ve moved from analyzing basic samples of mold to developing new molecules through innovative private-public partnerships. As bacteria are getting “smarter”, researchers spend hundreds of hours in the lab to develop new medicines to address drug resistance. With 34 antibiotics and infection preventing vaccines within the global pipeline, the opportunity to bring resistance under control is within reach.

In one of the most comprehensive analyses to date on the scope of drug resistance, the World Health Organization points out that there are major gaps in actions needed across all 6 regions in order to prevent the misuse of antibiotics and reduce the spread of antimicrobial resistance. Perhaps one of the most eye-opening findings is that few countries (34 out of 133 surveyed) have comprehensive national plans to tackle AMR. While antibiotic resistance is a serious global threat, it does not provoke the same sense of urgency for all countries.

It is evident that there is no “one-size-fits-all” approach, and that governments need to acknowledge the global principles for action and implement them at local level. There are some countries that are already leading the way, but not all may start from the same level playing field. In Europe, there are countries such as Sweden, the Netherlands or the UK, who have invested in taking concrete actions to meet ambitious targets on AMR. In Africa, for instance, there is a real need for more and better data to understand the magnitude of AMR, while China is looking to increase training for consumers and medical professionals on proper use of antibiotics. Furthermore, the IFPMA Health Partnerships Directory lists over 20 case-studies of collaborative initiatives to combat AMR.

These issues are at the top of agenda of the forthcoming UN High-Level Meeting on AMR, where UN member states will be summoned to maintain a strong political commitment to tackle this global health threat.

IFPMA has an event in the margins of this meeting, where we will discuss how the biopharmaceutical industry will deliver on the commitments laid down in the Declaration. Building on the Declaration, over a dozen leading biopharmaceutical companies have developed a roadmap which lays out a number of practical steps in four key areas: reducing manufacturing pollution; addressing inappropriate use; improving global access; and developing a broad R&D ecosystem. Without collective action and local implementation of plans, we cannot expect real change. But when the global community rolls up their sleeves, we are that much stronger in tackling AMR.

Useful links

Antimicrobial resistance: millions of lives and trillions of dollars? Jim O’Neill, Commercial Secretary to the UK Treasury, author of the Review on Antimicrobial Resistance

Tackling antimicrobial resistance Michele Cecchini, OECD Health Division

Tackling antimicrobial resistance

Multidrug-resistant_Klebsiella_pneumoniaeand_neutrophil.bmp
Multidrug-resistant K. pneumoniae bacteria interacting with blood cells

Michele Cecchini, OECD Health Division

Not so long ago, catching pneumonia with a bloodstream infection meant almost certain death: 90% of patients with this condition died. The discovery of penicillin by Sir Alexander Fleming in 1928 changed everything. Now more than 90% of patients with such a disease survive and many of the achievements of modern medicine are intrinsically based on our ability to prevent and cure infections. In addition, the prevention and cure of hospital-acquired infections have allowed the introduction of complex medical interventions such as organ transplantations, advanced surgery, and care of premature neonates.

All these medical achievements may be swept away by antimicrobial resistance (AMR). Microorganisms can learn how to withstand attacks by drugs.  By using antimicrobials incorrectly, we are helping them to do this quicker than they would do on their own. At the OECD, we have calculated that about 50% of all the antimicrobials prescribed by healthcare facilities in our member countries do not meet prescription guidelines. In healthcare services such as long-term care facilities and general practices up to 70% and 90% respectively of antibiotics may be prescribed for inappropriate reasons.

The extensive use of antimicrobials in high-density livestock agriculture and aquaculture is further sustaining the growth of AMR, particularly because, worldwide, up to 70% of antimicrobials are given to animals, often for no other reason than to make them grow more quickly.

The health and economic consequences of AMR are significant but will become enormous if no action is promptly put in place. The report produced by Jim O’Neill and his team provides an idea of what may happen if we do not take action soon. According to their estimates, up to 10 million people worldwide may die by 2050 due to six common diseases for which resistance is growing. This figure becomes even more significant (and alarming) by considering that many common infections, such as the main cause of community-acquired pneumonia, are not included in the analysis.

Healthcare budgets and the whole economy may be also put under stress. Patients developing resistant infections are more difficult to treat and we calculated that each patient costs up to an additional 40,000 USD due to increased medicalisation and time spent in hospitals. This figure is likely to double once indirect costs (e.g. absence from work) are taken into account.

The main issue now is to assess what we can all do to address AMR. The OECD Health Division is joining forces with our colleagues in the Directorate of Trade and Agriculture and with the Directorate of Science and Technology to provide sound evidence on the most effective and cost-effective policy options to tackle AMR. During the 2015 meeting of the Health Minsters of G7 countries, the OECD put forward five recommendations to best address AMR and its associated health and economic burden. In particular we believe that AMR can be successfully tackled only by:

  1. Strengthening existing surveillance and monitoring systems. Countries should further develop their surveillance systems to monitor AMR in the community setting (as opposed to hospitals) and to increase the number of microorganisms covered. We also need better information on antimicrobial prescribing practices.
  2. Adopting a globally agreed set of measurable targets on AMR incidence and efficient antibiotic use. Measurement of these targets should be integral part of a continuous evaluation processes.
  3. Strengthening ongoing efforts to rationalise antibiotics use and prevention of AMR spread in the human and livestock sectors. Rational utilization of antimicrobials includes both decreasing inappropriate use and ensuring access to high-quality drugs when needed. Successful and efficient interventions should be upscaled at the national level and across countries.
  4. Fostering the research and development of new antimicrobial therapies. Investments to develop new antimicrobials should be delinked from expected sales through appropriate economic incentives. Knowledge-sharing, for example, through global research platforms, should be encouraged as a cost-effective approach to research and innovation.
  5. Increasing coordination between partners to upscale efforts into a true global action. Countries’ action plans should be designed to reflect international standards and by adopting a ‘one-health’ approach. Coordinating strategies and best practices with other key partners would offer an opportunity to upscale efforts in an efficient fashion.

The final report of the Review on AMR led by Jim O’Neill discusses ten specific interventions that the UK and other countries should put in place to tackle AMR. Such actions are very much aligned with the five-pronged approach that we propose and with the WHO Global Strategy for Containment of AMR. The next step is to tailor these actions to the specific context and challenges of the different countries. The OECD can provide a forum where governments can discuss, develop and coordinate new strategies for prudent antimicrobials use in human medicine and agriculture as well as coordinate common strategies to incentivize the research and development of new antimicrobial therapies.

The OECD is putting in place a comprehensive programme of work on AMR, ranging from identifying the most cost-effective strategies to tackle AMR in humans to curbing unnecessary antibiotic use in agriculture. Some of the early results of this work, specifically on promoting the rational use of antimicrobials in humans, will be discussed during the 2017 OECD Health Ministerial meeting. OECD is ready to stand next to Member Countries and other key partners to move forward in the fight against AMR.

Useful linksantibiotic consumption

Antimicrobial Resistance in G7 Countries and Beyond G7 Health Ministers Meeting, Berlin, 8 October 2015

OECD Workshop: Economics of Antimicrobial Use and Resistance in the Livestock Sector 12 October 2015

Antimicrobial resistance in G7 countries: OECD Policy Brief

Antimicrobial resistance: millions of lives and trillions of dollars?

AMR reportJim O’Neill, Commercial Secretary to the UK Treasury

After I was appointed chair of the Review on Antimicrobial Resistance, one of the first questions I set out to answer was what would be the impact if no steps are taken to tackle rising resistance. While we can never know exactly what would happen in the future, I felt that any debates about the cost or difficulty of dealing with resistance should be informed by the far greater costs of inaction. Already resistant infections are estimated to kill at least 700,000 people a year, and in the United States alone they cost 20 billion USD in additional healthcare costs. We hired the consultants KPMG and RAND to examine what would the world look like in 2050 if we did not control resistance and to compare this to what would happen if resistance was tackled properly.

They both took current levels of hospital acquired infections for klebsiella pneumoniae, e. coli and  staph aureus, as well as total infection rates for TB, HIV and Malaria, and examined what would happen if resistance rates in these areas rose to 40 percent. This would mean that the first line treatment would fail 40% of the time. This figure was chosen as it was similar to the rates of k. pneumoniae that are resistant to carbapenems in parts of southern Europe, it is also similar to rates found for methicillin resistant staph aureus (MRSA) and multidrug-resistant TB (MDR-TB) in some parts of the world. As part of their research they presumed that a person with a resistant infection in the future would have the same outcome chances as someone today who gets a resistant infection, the levels of resistance would simply rise. They also presumed that rates of hospital acquired infections would double as people would carry the infections for longer making it easier for them to spread.

What the researchers found, using the above assumptions, is that if we do not take the appropriate steps to stop drug-resistant infections, the death toll could rise from 700,000 today to 10 million by 2050. This would mean that a person would die every three seconds from these six drug-resistant infections, and more people would die than are currently killed by cancer. The consequences of inaction would therefore be huge. KPMG and RAND, then fed these deaths into an economic model for what the world would look like by 2050; similar to the model that I used to make my BRICs prediction 15 years ago. The only change they made in their standard assumptions was that people who would die of AMR would no longer be able to work and consume goods. They ignored the impact of people being sick for longer, the indirect costs such as surgery being more complicated, the healthcare costs on society, the disruption to a family that can be caused by illness, and anything else that could cause productivity to change from resistant infections. Despite these conservative assumptions they found that over the next 35 years resistance would knock 100 trillion USD off the world’s production if we do not act to stop AMR. To put that in context that is more than the UK is expected to produce between now and 2050, and more importantly is far greater than the cost of tackling the problem.

Last week I had the pleasure of releasing the Review on AMR’s final report, where I highlighted ten interventions that the world needs to take to tackle resistance. The most important four being: first, to introduce rapid diagnostics so that doctors know whether or not a patient needs an antibiotic before prescribing them. Second, we need public awareness campaigns so that people know what resistant infections are and how to prevent them. Third, we need to find better incentives for people who come up with new drugs so that it is profitable; there has not been a new class of antibiotics since the 1980s. In order to tackle drug resistant infections we need to change that. Finally, we need reduce the amount of antibiotics we give out in agriculture. At the moment some farmers give out antibiotics to healthy animals so that they grow faster, and the whole of society picks up the cost of this though resistance. This is not acceptable; I am therefore delighted to see that the OECD is taking the lead on research into how to curb unnecessary antibiotic use in agriculture. More needs to be done to prevent this.

When costing our interventions my team and I estimated that it would cost up to 4 billion USD a year to avert this global catastrophe. I no longer work in investments, but spending  4 billion USD to prevent a crisis that will cost trillions and kill 10 million people a year is excellent value for money. From pharmaceutical companies to farmers, and from states to individuals, we all need to start acting now before it is too late.

Useful links

Antimicrobial Resistance in G7 Countries and Beyond G7 Health Ministers Meeting, Berlin, 8 October 2015

OECD Workshop: Economics of Antimicrobial Use and Resistance in the Livestock Sector 12 October 2015

Jim O’Neill will be participating in the Meeting of the OECD Council at Ministerial Level (MCM) on 1 and 2 June 2016, under the chairmanship of Chile, with Finland, Hungary and Japan as Vice-Chairs.