It has been three years since economist Lord Jim O’Neill sounded this stark warning in his government-commissioned report on AMR but, in October 2019, a follow-up review published by Chatham House, confirmed that global progress is flagging in crucial areas
Members of the general public are becoming more aware of AMR — a 2018 World Health Organization study confirmed that 125 countries are undertaking drug resistance awareness campaigns — and their involvement in prevention and infection control will be a core part of tackling it
. However, education and behavioural change can only go so far. We need new antibiotics and diagnostic tools, but leading pharmaceutical companies and biotechnology firms are faltering in their projects to develop new drugs, and research and development in rapid diagnostics is far from the level it should be
The scale of this challenge requires government mandates, and public and private investment at a global level. To achieve this, Lord O’Neill recommended a global market entry reward — a scheme that rewards innovation, but de-links price and sales volume from overall compensation. He suggested a levy on pharmaceutical companies to pay for this scheme and yet, at time of publication, it remains unfunded.
Failure to launch
In 2019, the UK government has twice announced a scheme to creatively compensate pharmaceutical companies for developing new antibiotics through subscription (a payment according to patients covered rather than units sold)
. However, the government has disclosed neither the scope of the scheme, nor how it will engage with the companies. To be effective, this type of scheme needs the participation of multiple countries and, so far, a coalition of the willing has failed to materialise. All the while, big pharmaceutical companies and leading biotechnology firms continue to disinvest in antibiotic research and development. The AMR Industry Alliance — a group of 100 companies from the life-science industry, formed to respond to the call to action against AMR — seems just an empty vessel. This has done little to stimulate antibiotic research and development since it was launched in 2017.
Many endeavours are not receiving the public and/or private investment they need
New antibiotics may be a pipe dream, but there are exciting new technologies in the field of diagnostics to reduce overuse of antibiotics, although the picture is far from rosy. Lord O’Neill’s report called for antibiotics to be prescribed only after biological tests; this call has not been transformed into policy. Many endeavours are also not receiving the public and/or private investment they need.
Push-and-pull incentives (where funding can be given or taken away) for diagnostics have never been more crucial. In 2015, a study showed that of the 86 million US patients who were thought to have a respiratory issue that antibiotics could not successfully treat, 27 million were still given antibiotics unnecessarily
. This won’t change without new tests that differentiate bacterial and viral infections.
In 2018, a study suggested that community pharmacies can beneficially deliver effective point-of-care testing for respiratory tract infections using tests for C-reactive protein
. However, as Chatham House’s progress report states: “While there has been some progress … for the most part, there is no diagnostic test that meets the desirable target product profile that would enable prescribers to avoid empirical prescribing
In other words, diagnostic tests are not yet sophisticated enough, so incentives to facilitate mandatory use of these diagnostic tests are “secondary to the issue of their availability”.
Some argue that experienced clinicians and infectious disease specialists can dramatically reduce unnecessary antibiotic use by relying on their training and experience, and following guidelines. Perhaps, but in the UK, where doctors and nurse practitioners have less than eight minutes with a patient in GP surgeries, accurate, fast tests would make a dramatic difference.
Pharmacists and diagnostics
Increased use of point-of-care tests in pharmacies could reduce the number of patients needing to see a consultant and enable more rational use of antibiotics
. There are significant savings in getting a diagnosis right the first time, from reduced repeat patient visits to reduced hospital admittance. New susceptibility tests, that identify which treatment a patient’s infection will be susceptible to, will help people get the right antibiotic the first time around, and help to measure and track resistance.
Simply lowering or limiting antibiotic prescriptions across the board is too blunt an instrument
In the UK, urinary tract infections (UTIs) caused by antibiotic-resistant bacteria are common
. UTIs are major drivers of antibiotic prescribing in primary care, yet testing still isn’t the norm. A study published in 2019, found that almost 86% of patients in England, between 2011 and 2015, received antibiotics for UTIs on the day they were diagnosed; and 83% of those had no evidence of collecting a urine sample for microbiological testing
. The study authors highlight that these patients received trimethoprim (57%) or nitrofurantoin (24%), in line with guidelines. However, resistance to trimethoprim became so common that the guidelines were changed to assign nitrofurantoin as the first-line antibiotic to use
. Even a small number of patients receiving inappropriate first-line drug treatment could foster resistance in Escherichia coli (a common cause of UTIs), a pathogen with major consequences for hospitalised patients.
Simply lowering or limiting antibiotic prescriptions across the board is too blunt an instrument and can even cause harm when patients miss out on essential antibiotic treatment. The syndromic approach to diagnosis needs to be challenged. We must carve out a long-term path towards the more intelligent use of antibiotics — a future of targeted treatments and clinical decisions based on test results. New, fit-for-purpose point-of-care tests will be essential to better deploying antibiotics and slowing resistance.
Eyes on the prize
The good news is there are signs of progress. Exciting new diagnostic technologies are in development, but, at this critical juncture, they need more support and investment.
The Longitude Prize, originally launched in 1714 to find a way of determining a ship’s longitude, has returned 300 years later; this time to aid the search for an affordable, accurate, fast and easy-to-use test for bacterial infections.
Pharmaceutical developers and diagnostic makers need to know their innovations will be rewarded and procured.
An example of the type of test we’re encouraging, so long as it meets the prize criteria, is well illustrated by one of our US entrants ‘FebriDX’. The tool, still in the US Food and Drug Administration approval process, uses a capillary blood sample to identify and differentiate a clinically significant immune response to viral and/or bacterial acute respiratory infection, and results are available within ten minutes.
Pharmaceutical developers and diagnostic makers need to know their innovations will be rewarded and procured. They need assurance that thought-leaders and the NHS will pursue policy that gets diagnostics into GP surgeries, hospitals and pharmacies, when they meet needs.
We need not only a policy shift, but a cultural shift in healthcare, to ensure diagnostic tests have been performed whenever possible before an antibiotic has been prescribed. This will only be practical if rapid, reliable and affordable diagnostics are readily available at the point of care.
Daniel Berman, lead, Longitude Prize; head, Global Health, Nesta Challenges
 O’Neill J. Chatham House. 2016. Available at: https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf (accessed December 2019)
 Clift C. Chatham House. 2019. Available at: https://www.chathamhouse.org/publication/review-progress-antimicrobial-resistance (accessed December 2019)
 World Health Organization. 2019. Available at: https://apps.who.int/gb/ebwha/pdf_files/WHA72/A72_18-en.pdf (accessed December 2019)
 McCoy M. Chemical and Engineering News. 2019. Available at: https://cen.acs.org/business/finance/Antibiotic-developer-Achaogen-files-bankruptcy/97/i16 (accessed December 2019)
 Department of Health and Social Care. 2019. Available at: https://www.gov.uk/government/news/development-of-new-antibiotics-encouraged-with-new-pharmaceutical-payment-system (accessed December 2019)
 National Institute for Health and Care Excellence. October 2017. Available at: https://www.nice.org.uk/news/article/antibiotic-resistance-is-now-common-in-urinary-tract-infections (accessed December 2019)