By Aiden Hannah, Research Analyst, and Samrina Bhatti, Manager, Deloitte Centre for Health Solutions

Antimicrobial resistance (AMR) threatens the effective prevention of an ever-increasing range of infections caused by bacteria, viruses, parasites, and fungi. The World Health Organisation (WHO) has declared AMR as one of the top 10 global public health threats facing humanity. While this threat has been widely acknowledged globally, the response to date has been episodic and uneven, resulting in global inequities in AMR. Moreover, the cost to the economy is significant, as in addition to death and disability, AMR leads to prolonged illness, longer hospital stays, the need for more expensive medicines and financial challenges for those affected.¹ Unless concerted action is taken, AMR is predicted to cause 10 million deaths annually by 2050, at an estimated economic cost of $100 trillion.² In this week’s blog we explore the vital role that rapid diagnostic devices can play in tackling AMR, through early detection of infection and identification of effective therapeutic management.

What is AMR and why is it a growing threat to public health?

AMR arises when the organisms that cause infection acquire ways to survive treatments. The term antimicrobial includes antibiotic, antiprotozoal, antiviral, and antifungal medicines. AMR develops naturally over time but is increased and accelerated by factors such as poor infection control, lack of clean water and sanitation and global trade and travel. A significant driver is the unnecessary use of treatments, with up to 50 per cent of all antibiotic prescriptions ineffective or not required.³ Antibiotic resistance is a particular concern as many medical advances, for example, organ transplantation and cancer chemotherapy, need antibiotics to prevent and treat the bacterial infections that can be caused by the intervention. Without effective antibiotics, even routine operations could become high risk procedures.⁴ Solutions include robust antimicrobial stewardship, proactive infection prevention and outbreak surveillance, fast diagnosis, and appropriate treatment.

How can rapid diagnostic devices help promote antimicrobial stewardship?

The importance of rapid and accurate infection diagnosis is important in avoiding unnecessary use of antimicrobial therapies, but identifying a cost-effective and easy test for bacterial and viral infections has proved elusive.⁵ This was emphasised in the O’Neil report on AMR published in 2016 which, among other things, called for the review, development, and promotion of rapid diagnostics to reduce unnecessary antimicrobial use and improve antimicrobial stewardship.⁶ The AMR review noted that it was ‘unacceptable that much of the technology used to inform the prescription of important medicines like antibiotics had not evolved substantially in more than 140 years’. It recommended for ‘rich countries to make it mandatory that by 2020 the prescription of antibiotics should be informed by data and testing technology wherever available and effective in informing the doctor’s judgement to prescribe’. It also suggested the need for funding to stimulate a diagnostic market for the development of new, rapid diagnostics to cut unnecessary use of antibiotics.⁷

The UK government’s response in 2016, included investments in improving laboratory capacity, international surveillance systems and a global AMR innovation fund; as well as incentives to develop innovative diagnostic tools and initiatives to promote the use of diagnostics to drive appropriate prescribing in the NHS.⁸ Subsequently following recommendations from a 2019 Health and Social Care Committee inquiry on antibiotic resistance, the government concluded that a headline ambition of its vision for AMR in 2040 was ‘to have new diagnostics, therapies, vaccines and interventions in use, together with a full AMR research and development pipeline for antimicrobials, alternatives, diagnostics, vaccines and infection prevention across all sectors’.⁹ At the same time, the government’s ‘Tackling AMR five-year action plan’ set out a number of strategies, including a requirement to report on the percentage of antibiotic prescriptions supported by a diagnostic test or decision support tool by 2024.¹⁰ 

What are the main challenges that need to be overcome?

Approximately 70 per cent of clinical decisions are influenced by in-vitro diagnostics (IVDs), yet only one per cent of the NHS’ budget is spent on IVDs and there has been significant under investment in diagnostics (technology, infrastructure, and people) over many years.¹¹ Gold-standard culture-based methods of infection detection and susceptibility testing in clinical practice have typical turn-around times of at least 24 to 48 hours, and so do not support early targeted treatment selection. There are many devices already available that support more rapid but accurate methods of bacterial detection and identification, such as mass spectrometry and polymerase chain reaction (PCR), however there are still a number of limitations to the use of these technologies, including:

• • high equipment costs
  • being designed for operation in laboratories by expert staff
  • requiring complex sample processing, often still with a culturing step
  • as is the case with real time PCR, requiring separate tests to identify the bacteria and antibiotic susceptibilities.

As noted in the government’s Tackling AMR five-year action plan, regulatory requirements make it difficult to assess the value of any new diagnostic test to the overall AMR agenda and can delay adoption. The strategy proposes establishing clearer guidelines and new methods for demonstrating the value of AMR diagnostics (including case studies, pilot studies and cost-effectiveness models) to help change the behaviour of health commissioners and practitioners, and increase adoption of new diagnostics. It also makes several commitments, such as developing alternative funding models for faster diagnostics that support targeted treatment and streamlining the regulation process.¹²

The onset of the COVID-19 pandemic while switching attention and resources to developing and approving tests for the SARS-CoV-2 virus, has helped raise the profile of the importance of point of care testing (POCT) with clinicians and the public There is now an opportunity to capitalise on this and re-energise the implementation AMR strategy.

What lessons can be learned from COVID-19 testing?

In August 2020, the Association of British Healthcare Industries (ABHI) Diagnostics group noted that Testing for SARS-CoV-2 and screening for COVID-19 antibodies are widely acknowledged as key tools to manage both the human and economic impact of the global coronavirus pandemic. While the Government acknowledged that the UK went into the pandemic with a shortfall in testing capacity and capability due to less investment in diagnostics compared to other countries, strong partnership working between industry and Government quickly rectified this situation, leading to an acceleration in new ways to conduct tests.¹³

The proliferation of testing for SARS-CoV-2 during the COVID-19 pandemic has significantly increased awareness, globally, of the role of diagnostics in protecting the nation’s health including the importance to detect diseases as early and accurately as possible and accurately to guide the right treatments. Historically, low-cost rapid infection tests such as dipstick urine tests and other lateral flow tests are typically less sensitive, less specific, and provide less diagnostic information than gold-standard laboratory tests. However, as seen during the COVID-19 pandemic, these tests can have widespread adoption due to their improved ease of distribution, access, and use.

Emerging technologies for rapid bacterial detection include a wide range of biosensors (focused on either molecular detection such as DNA, whole bacterial cell detection, or other biomarkers of infection) and AI enhanced diagnostics such as microscopy techniques.  This is an area of much ongoing innovation, incentivised by several funding competitions and prizes (for example, the Longitude prize and CARB-X diagnostics round).^{14 15} Ideally, new technologies would enable both the rapid determination of what agent is causing the infection, and additionally identify any resistances that are present to ensure any treatment required is prescribed as soon as possible. Furthermore, a technology that is portable, low-cost and resource efficient would have the greatest global impact, ensuring fair access across geographies and settings of use.

Adopting innovative funding models for diagnostics, such as the subscription-based model announced for antimicrobials in 2020, could be a key driver of the development and subsequent adoption of innovative technologies.¹⁶

Conclusion

AMR has both significant economic and humanitarian consequences.  Expanding the use of rapid diagnostics for infection globally presents an opportunity to combat rising antimicrobial levels and improve patient outcomes. This will, however, require enhanced investment both in early-stage research and healthcare system adoption of diagnostic devices. While potentially having higher upfront costs than antimicrobial drugs, diagnostic devices have the ability to enable greater long-term savings and, ultimately, save lives by increasing the lifespan of therapeutics.

Samrina Bhatti, MRPharmS, PGDipGPP, Manager

Sam is a national award-winning pharmacist with local, national and international experience. Prior to joining the Centre, Sam was working alongside the Chief Pharmacist at Bart’s Health delivering trust-wide projects in service development and implementation. Prior to this Sam was the NHS England Chief Pharmaceutical Officers’ Clinical Fellow at Specialist Pharmacy Service, where she led various national projects on medicines use and digital healthcare. Sam is part of the global commonwealth health partnerships, an NHS England Clinical Entrepreneur, and a pre-doctoral fellow at Health Education England undertaking a PGCert in Healthcare Research Methods. Sam is also an associate of the Faculty of Clinical Informatics and Institute of Healthcare Management and has a Master of Pharmacy from King's College London and Diploma in General Pharmacy Practice.

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Aiden Hannah, Research Analyst

Aiden has a background in physics and biomedical engineering, and a strong technical knowledge of diagnostics and digital healthcare. Most recently working as an academic researcher, he undertook a range of multidisciplinary projects involving close collaborations between MedTech companies and clinicians; supporting the development of novel biosensors and low-cost diagnostics, including clinical trial design and conduct. Aiden has focused on the health technology investment pipeline and the medical device regulatory processes as part of his doctorate industry placements.

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¹ https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

² https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/784894/UK_AMR_5_year_national_action_plan.pdf

³ https://pubmed.ncbi.nlm.nih.gov/29991221/

⁴ https://www.gov.uk/government/collections/antimicrobial-resistance-amr-information-and-resources

⁵ https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf

⁶ https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf

⁷ Ibid.

⁸ https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/553471/Gov_response_AMR_Review.pdf

⁹ https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/773068/antimicrobial-resistance-government-response-to-hscc-inquiry.pdf

¹⁰ https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/784894/UK_AMR_5_year_national_action_plan.pdf

¹¹ diagnostics-a-future-roadmap.pdf (abhi.org.uk)

¹² https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/784894/UK_AMR_5_year_national_action_plan.pdf

¹³ https://www.abhi.org.uk/media/2768/diagnostics-a-future-roadmap.pdf

¹⁴ https://longitudeprize.org

¹⁵ https://carb-x.org/portfolio/portfolio-companies/

¹⁶ https://www.gov.uk/government/news/world-first-scheme-underway-to-tackle-amr-and-protect-uk-patients