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Tackling antimicrobial resistance on multiple fronts

An urgent change of direction is needed in how we respond to AMR

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With an estimated 25,000 deaths in Europe alone and one person dying every 15 minutes in the US because of drug-resistant bacterial infections, antimicrobial resistance (AMR) is undoubtedly one of the greatest public health challenges of our time.

In 2013, England’s then Chief Medical Officer, Professor Dame Sally Davies, publicly likened it to a “ticking time-bomb” and warned that routine operations could become deadly due to untreatable infections in as little as 20 years.

Today, in 2019, some countries are having success in transforming their thinking about antibiotics, viewing them as a resource to be preserved rather than the default treatment option.

Simply focusing on reduction of volume of antibiotics will not be enough either. Recent studies, like that of Public Health England, confirm that knowing when to use antibiotics is becoming even more important and while behaviours are shifting in the right direction, they also demonstrate that sanitation, infection control and awareness can only go so far.

An urgent change in direction

Despite these public health changes, resistance levels continue to rise and now alarm bells are sounding for the future of live-saving treatments like chemotherapy for cancer. Even as the need for new diagnostics and antibiotics grows, we know that the markets for these products is in dire straits. We need to see an urgent change of direction in how we respond to AMR; it must be tackled on multiple fronts.

No new classes of antibiotics have been discovered since the 1980s and the market incentives for research and development in this area are becoming more and more limited.

Government investment is increasing in early phases of research through mechanisms such as CARB-X, which supports companies that are identifying and testing new antibiotics, but even with this de-risking, big pharma continues to disinvest from this space and there have been high profile bankruptcies of biotechs. Vaccines to reduce bacterial infections are also urgently needed – although these are also not seen as lucrative enough to attract investment.

While there is no panacea to the challenges we face, a key part of responding effectively to the situation is to accelerate the development of life-saving diagnostic devices that will revolutionise current healthcare practice when it comes to antibiotic use. Recent new data from the US Center for Disease Control report found that around 30% of all antibiotic prescriptions in the US are unnecessary.

From chemists to doctors’ surgeries, medical practitioners, particularly at the primary care and outpatient levels, need the tools to enable them to be more ‘AMR-Smart’ (a point backed by the latest World Bank report, Pulling Together to Beat Superbugs, on the knowledge and implementation gaps in addressing antimicrobial resistance).

The development of novel antibiotics will be essential in providing a last line of defence against rapidly evolving pathogens. However, given that misuse and overuse of antibiotics are drivers in the rise of superbugs, we need to also focus on prescribing and empowering better clinical decision-making.

Waiting 2-3 days for results from labs puts doctors and pharmacists on the back foot in the management of AMR – tests should take minutes instead of days. Given this situation, it’s perhaps no wonder that ailments like sore throats are still mistreated with antibiotics, when they are viral.

Innovation is key

Innovation in this area is key to changing course, instead of just kicking the proverbial can down the road. Indeed, rapid point-of-care (POC) diagnostic devices would give pharmacists and clinicians alike a better means of testing patients. In turn, this would enable better decision-making about antibiotic use – especially in ensuring that the correct, most effective antibiotic is dispensed first time around.

Rapid tests on the frontline would help reduce bloodstream infection admissions to hospitals and the subsequent transfer of bugs to immunocompromised patients on wards, like those receiving cancer treatment.

From a UK perspective, the challenge of getting the right antibiotic the first time around is exemplified in the current treatment of urinary tract infections (UTIs). In a British context, the majority of UTIs are due to Escherichia coli (E. coli). If we treat E. coli infections incorrectly, over-prescribing first-line antibiotics when some patients may already have resistant infections, we will effectively create a superbug; that is an infection that is particularly dangerous in many circumstances, especially in hospital.

The good news is that advanced technical work is ongoing around the world to develop new technology and adapt existing tools so that they can diagnose bacterial infections. Indeed, the innovations in the race to win the Longitude Prize, an £8m challenge prize to accelerate the development of a rapid, affordable point-of-care diagnostic test to reduce overuse and misuse of antibiotics, have identified promising tests.

Some can distinguish a bacterial infection from a viral infection on the spot in formats that are as easy to use as a pregnancy test. One competitor is using a camera that compares a single image of an infection against an AI-enabled database to precisely and quickly identify pathogens.

The downside is that while there are a lot of new technologies that are getting close to market, that market, as it stands today, is dysfunctional, preventing innovation breaking through. Developers and investors are not convinced that health systems and individuals will be ready to buy new diagnostics.

Simply put, the current economic set-up makes development of both diagnostics and antibiotics unviable. In terms of diagnostics, even if you have a good idea and a good prototype, attracting the financing to turn it into a product is difficult because the numbers just don’t add up.

The Longitude Prize

From a design perspective, we know that a key challenge for those developing tests that can be used in universal settings (that is to say, not just in wealthy countries) is to know which antibiotics will be effective against a given pathogen. Developing a test to assess antibiotic susceptibility is particularly challenging because a pathogen must be given the chance to grow before we can determine if an antibiotic will work.

One of the key criteria set out in the Longitude Prize is that the time between taking the sample and the result is a maximum of 30 minutes, a tough request considering the limitations of existing technology. Another challenge is miniaturisation: creating a sophisticated test that can perform like a pregnancy test or rapid malaria test is difficult, but not impossible.

The right incentives

So called ‘push funding’ plays a fundamental role in facilitating research and development that enables innovators to develop their products, but at the same time, the market-appropriate ‘pull’ incentives also need to be in place.

A recent, worrying example of the market dysfunction is that the most recent antibiotic introduced in the UK only had sales of £200,000 for the year – this sends a signal to the pharmaceutical industry that antibiotics are not highly valued. The situation may be less dire for diagnostics, but the lesson remains.

The undervaluing of antibiotics in the UK is being addressed in a pilot project that uses a Netflix-like subscription model to negotiate service contracts that guarantee income for pharma companies that sell new antibiotics to cover a population over a period of years.

The payments in these contracts will be based on the value of the products to health systems rather than on the volume of pills sold. This pilot project is a good start in demonstrating that new antibiotics will be fairly compensated, but more efforts are needed to stabilise the antibiotic market.

We argue that ‘delinking’ strategies like those being trialled by the UK government would have a greater chance of success if they went beyond national confines and were plugged into a cross- sector, cross-border, global agenda.

At Nesta Challenges, home to the Longitude Prize, we have long promoted a holistic approach, actively reaching out to a range of disciplines and sectors, across countries, and encouraging new collaborations between innovators and other stakeholders to make sure products and services actually reach people that can benefit from access.

An international AMR Fund

That’s why a new funding mechanism is needed, one that will be initiated and backed by multiple players, including decision-makers and influencers in pharma and healthcare who know the scale of the challenges we face. We already have effective mechanisms that fund access to vaccines, TB, HIV and malaria. Why not an international AMR Fund to support uptake of products to tackle AMR too?

Such an investment mechanism would provide the initial funds to make the market attractive and viable to developers, and specifically money to subsidise or purchase innovative products. After all, one thing that is certain is that funding, support and market access are a minimum requirement for healthcare innovations to reach patients. Only when the market is shored up with more public funds can we initiate the necessary paradigm shift when it comes to tackling AMR.

Daniel Berman is Head of Global Health at Nesta Challenges

27th January 2020

Daniel Berman is Head of Global Health at Nesta Challenges

27th January 2020

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