Point-of-Care Armory against Antimicrobial Resistance

We spoke to Paul Chapman, member of the Longitude Prize advisory panel, about the Prize for a solution to antimicrobial resistance.

The UK government Review on Microbial Resistance has estimated that drug-resistant infections could lead to an extra 10 million deaths across the world by 2050. Subsequently, the race is on for the £10 million Longitude Prize to develop a cost-effective, accurate, rapid, and easy-to-use diagnostic test for bacterial infection so that health professionals worldwide can administer the right antibiotics at the right time.

Over 100 teams have registered to take part in the Longitude Prize, which was developed and is run by innovation charity Nesta. It was launched by the Prime Minister at G8 in 2013, and through the Department for Business, Innovation and Skills is being supported by Innovate UK as a funding partner. So far, eight teams have already submitted entries to win.

The prize opened in 2014 after a public vote held by BBC Horizon chose anti-microbial resistance as the focus for the prize. In addition, 78 per cent of 2,000 UK survey respondents identified anti-microbial resistance as a public health concern. In the survey, anti-microbial resistance was perceived as a threat to public health, second only to cancer. The threat of existing antibiotics no longer working effectively was also of great concern, second only to a terrorist attack. This finding echoes the World Health Organization’s declaration that antimicrobial resistance is a worldwide threat.

Inappropriate use of antibiotics

The use of antibiotics to prevent or treat infections is widespread both in healthcare facilities and the community.  It is regularly used in prophylactic doses for common surgical procedures such as Caesarean sections and appendectomies, or for dental surgery. Antibiotics are also prescribed to patients prior to surgery to prevent an opportunistic infection. However, there is a marked tendency to use antibiotics inappropriately, leading to a very real threat of antimicrobial resistance.

One major problem, according to Paul Chapman, European & UK Patent Attorney at Marks & Clerk LLP and member of the Longitude Prize advisory panel, is that broad spectrum antibiotics are used all too often - sometimes in cases where they shouldn’t be, such as to fight a viral infection; antibiotics are ineffective against viral infections. He explains, “When a patient comes in to the doctor’s clinic complaining of a sore throat, the doctor can take a swab of the throat, put the swab on a petri dish, and wait a week or two to accurately determine if it is a viral or bacterial infection.” This often isn’t good enough for patients. “Patients come in to the doctor’s office expecting to be treated. They come in expecting the doctor to prescribe medication.  In a lot of ways, doctors feel pressured to prescribe broad spectrum antibiotics,” says Chapman.

Broad spectrum antibiotics kill a whole range of different kinds of bacteria. Ideally, antibiotics are effective because they are a treatment targeted to kill specific classes of harmful bacteria while leaving other ‘good’ bacteria unharmed.  When physicians are unsure as to the kind of bacteria a patient is infected with, they often prescribe broad spectrum antibiotics – a volley of shots – and hope that at least one will hit the target class of bacteria that has caused the infection. Such indiscriminate use of broad spectrum antibiotics promotes bacterial resistance to antibiotics.

While there are tests to determine whether a particular infection is bacterial or viral, the tests that are currently available may take days to produce results. They can also be costly. There is another type of test that produces results in less time, which is used in developed countries with sophisticated health care systems – it is DNA testing of bacteria in order to prescribe a specific and appropriate class of antibiotic.

Chapman puts this into the context of a developing country: “There may be just one laboratory where a bacterial culture can be grown and there may be just one hospital where DNA testing of bacteria can be performed.”  He also explains another situation that demonstrates the problem regarding the cost of bacterial testing:  “In developing nations, antibiotics are cheap.  They can be obtained over-the-counter, sometimes even without a prescription. If the test costs more than the antibiotics, people will opt to take antibiotics instead of doing the test.”

A snowballing problem

Chapman explains the threat of antimicrobial resistance is a continual “snowballing of factors” that may result in creating a scenario similar to the pre-antibiotic era when the most common infections would kill thousands. He says, “The bacterial ability to rapidly adapt and mutate is inherently the unfortunate nature of the beast – this is how bacteria survive.” Combine this with the fact that new antibiotics or new classes of antibiotic drugs haven’t been developed for decades. “The development of new classes of antibiotics is akin to developing new tools in our armoury, something which has largely been neglected", says Chapman.

Of great concern is that if “new tools in our armoury” continue to be neglected, diseases which we can currently treat, may become untreatable in the future. For example, it is recognized that antibiotic resistant tuberculosis is becoming an increasing risk. According to Chapman, “Most people think that tuberculosis is a health concern solely of underdeveloped and developing nations. The truth is that the tuberculosis bacterium is becoming prevalent again and this time it is resistant to the antibiotics that were once used to effectively eradicate it from developed countries.”

The growth of the tuberculosis bacteria in the lungs is slow and often goes undetected for long periods of time. Efficient air travel has made it possible for people from developing nations who are infected with the tuberculosis bacteria to enter developed countries and unknowingly spread the bacteria there.  For this reason, the resurgence of tuberculosis is the prime example of the global threat of antimicrobial resistance.

To address the problem of rapidly growing antimicrobial resistance, the Longitude Prize has determined that a small device or test has to be developed, which can be used by any doctor or nurse prescriber in a clinic or surgery anywhere in the world - in a city or in the bush. “It is important that the test or device be available for use at ‘point-of-care’ – meaning, at the site where the patient comes in for treatment,” emphasizes Chapman. He adds, “The drive at this time is to get a diagnostic tool at the point-of-care that can rapidly and accurately determine if the infection is bacterial or viral so that appropriate treatment can be administered.”

Challenges for pharma

Chapman states his opinion on the challenge posed by the global problem of antimicrobial resistance to pharmaceutical companies: “Bringing products to market is costly and pharma companies developing them must be able to recoup the cost and make a profit at the end of the day.” Antibiotics don’t make much profit for drug companies: there is such a high demand for antibiotics in the market due to the vast need for them, but there isn’t much market profitability in developing them.  The more cheaply an antibiotic drug is priced, the more saleable it is.

One cause for hope is the number of patents filed in this area - since 2009, 332 patent families have been filed. This indicates an increasing interest in the field. Another cause for hope is the notable leadership of the UK in the drive against antimicrobial resistance. It is second only to the US in terms of number of patent applications filed in the field of antimicrobial resistance. Furthermore, alongside the existing teams working on diagnostics development, evidenced by patents being filed, the Longitude Prize and other campaigns aim to tempt new innovators into this area of innovation.

Chapman attributes the UK’s leadership in this field to the UK government’s recognition of the issue: “The government’s interest encourages scientists to find solutions, as does the fact that the UK government provides funding to universities to do research in this area.” Although there is no government funding for private companies to develop the diagnostic tools, historically, small and medium-sized companies have been at the forefront of research and development, evidenced by the number of patents filed by such private companies.

Chapman is optimistic, highlighting that, “Worldwide, the growing number of patent applications is a sure indicator that it is an area that needs innovation and development.”  He is confident that the Longitude Prize initiative will prompt other players in the pharma industry to “jump on the bandwagon” - if at least one company develops a diagnostic tool, other companies may want to do something similar.

The heat is on

Competitors now have 4 years to find a solution to the problem of antibiotic resistance. A successful test will need to:

  • Show when antibiotics are needed and if they are which ones to use;
  • Be accurate enough to inform treatment decisions;
  • Be affordable to everyone who needs it;
  • Provide a result within 30 minutes;
  • Be easy to use in any location, anywhere in the world;

There are submission windows to win the Prize every four months.The first team to successfully meet the criteria of the Longitude Prize wins. The prize will close on 31st December 2019 – although it could be awarded at any time. The heat is on!

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