Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip.

Overview of change

According to the World Health Organization (WHO), antimicrobial resistance (AMR) is one of the most urgent global health challenges for the next decade, alongside climate change.1 AMR can evolve in all groups of pathogens, including viruses, fungi, bacteria and parasites. Human, animal and environmental health are all interlinked when it comes to AMR.2–8  Cases of antimicrobial-resistant infections (including drug resistant tuberculosis, gonorrhoea and more common hospital infections, including from Escherichia coli) are increasing in the UK and worldwide, and sometimes can only be treated by antimicrobials of last resort.9–13 Following the 2016 O’Neill report, a 2018 Health and Social Care Select Committee report defined AMR as a ‘top five policy priority’.14 In 2019 the UK Government published a 20-year vision for tackling AMR and a 5-year action plan, which followed on from an earlier 5-year plan published in 2013.15–17 AMR is one of the Government’s priorities for the UK’s G7 presidency in 2021.18  A ‘One Health’ approach, focusing on human, animal and environmental health, underpins UK strategies against AMR.4,16

Opportunities and challenges to tackling AMR span creating alternative financing models to supporting antimicrobial discovery, developing new technologies to improve surveillance, ensuring better stewardship of antimicrobials, and improved infection prevention and control strategies in people and animals.

Challenges and opportunities

A continual supply of new antimicrobials (drugs) is required to overcome the inevitable resistance to existing ones.19 The economic model for drug development does not favour costly investments in developing new classes of antibiotics, which would be reserved as a last resort for treating infections. In the past year there have been a series of initiatives to incentivise the development of new antimicrobials. These include the launch of the AMR Action Fund, an international partnership between pharmaceutical companies, philanthropies, development banks and multilateral organisations aiming to develop between two and four new antimicrobials by 2030. The UK is also piloting a ‘subscription style’ payment model for antimicrobials development, with NHS investments paid in advance to pharmaceutical companies. The National Institute for Health and Care Excellence is currently exploring new models for the evaluation and purchase of antimicrobials.20–24 Further alternative funding models, including the creation of ‘challenge’ prizes, public-private and public financing options could also represent an opportunity for antimicrobial research and development.25,26

There are additional approaches to addressing the AMR challenge. Achieving a better understanding of the drivers of AMR is needed, including the underlying biological mechanisms.27,28 The development of new technologies (including those involving artificial intelligence) could facilitate the design of new antimicrobial drugs and the rational use of antimicrobials.29,30 Finally there needs to be more effective translation of new antimicrobial drugs from discovery to the clinic, equitable access to new antimicrobials, and the development of alternatives to antimicrobials (such as vaccines to prevent infections).31,32 All of these interventions need to be within a One Health context.

The development of diagnostic tools was one of the key recommendations in the O’Neill report. While portable and rapid diagnostic kits able to detect drug resistant infections are currently under development,33,34 little progress has been made overall and the majority of modern labs routinely employ diagnostic approaches based on laborious and low-tech methodologies.35,36 Better surveillance of resistance and stewardship of currently used antimicrobial drugs in humans, animals and the environment are essential to tackle AMR. Finally, infection prevention principles and practices and associated behaviours (including in healthcare settings) represent a potential solution to AMR: the £37 billion hospital funding programme announced by the Prime Minister in October 2020 provides an opportunity to design new wards and clinics with the aim of protecting against the transmission of multidrug resistant bacteria as well as airborne pathogens such as influenza virus and SARS-CoV-2.37,38,39

Key unknowns

Some experts suggest that COVID-19 is leading to better hygiene practices, that could potentially help in preventing the spread of infections (and therefore AMR).46,47 Others instead warn that the excessive use of disinfectants (including alcohol-based ones) could lead to more AMR infections, given the bigger environmental pressure for micro-organisms to survive.48

Another unknown is the contribution made by environmental contamination with antimicrobials and multidrug resistant bacteria (such as from industry, agricultural runoff or human sewage) to the development of AMR infections in human and animals.49,50 Some academics suggest that there is an opportunity to amend the Environment Bill to include commitments to tackling environmental contamination with drug resistant bacteria and antimicrobials.51

AMR is a global challenge, so continued and sustained global strengthening of capacities and capabilities (including in surveillance systems) are key. However, the impact of recent overseas development aid funding cuts on AMR research supported by the UK is unknown (see The Future of UK Research).

Key questions for Parliament

  • The 2016 O’Neill Review on AMR made 10 recommendations, including developing rapid diagnostics, increasing antimicrobial stewardship, promoting public awareness, improving hygiene practices, increasing funding and improving surveillance. What progress has the UK Government made against these recommendations?
  • e 20-year vision looks forward to a world where AMR is on the decline. What support to tackle AMR in low- and middle-income countries (including building surveillance systems) is included in the UK Government’s Foreign, Commonwealth and Development Office budget?
  • Did COVID-19 have an impact on the UK’s 5-year action plan (‘Tackling antimicrobial resistance 2019–2024’)?
  • Is there a potential for lessons learnt from COVID-19 to be applied to tackle AMR? These might include improved surveillance, building laboratory capacity, developing diagnostic tests and vaccines, encouraging academic/industry partnerships, and adapting the regulatory landscape around licensing.
  • Within the new hospital funding programme, are there enough resources to support improved infection prevention and control in hospital settings and, therefore, prevent AMR infections?
  • Are there enough measures to tackle AMR in the Environment Bill?
  • How will future UK trade deals impact AMR?

Likelihood and impact

A UN report has evaluated that AMR could cause at least 10 million deaths per year globally by 2050 if measures are not taken.52 By comparison, 2.73 million people have died so far during the COVID-19 pandemic. Overall: high impact, being felt now.

Research for Parliament 2021

Experts have helped us identify 30 areas of change to help the UK Parliament prepare for the future.

References

  1. WHO (2020) Urgent health challenges for the next decade.
  2. Pokharel, S. et al. (2020). Antimicrobial use in food animals and human health: time to implement ‘One Health’ approach.   Antimicrobial Resistance & Infection Control, Vol 9, 181.
  3. Graham, D. W. et al. (2019). Complexities in understanding antimicrobial resistance across domesticated animal, human, and environmental systems.   Ann N Y Acad Sci, Vol 1441, 17–30.
  4. UK One Health Report: antibiotic use and antibiotic resistance in animals and humans.  GOV.UK.
  5. Evans, N. et al. (2021). Reducing UK Antibiotic Use in Animals. 
  6. Dowling, A. et al. (2021). Reservoirs of Antimicrobial Resistance. 
  7. Woolhouse, M. et al. (2015). Antimicrobial resistance in humans, livestock and the wider environment.   Philos Trans R Soc Lond B Biol Sci, Vol 370, 20140083.
  8. Waseem, H. et al. (2018). Antimicrobial Resistance in the Environment.   Water Environ Res, Vol 90, 865–884.
  9. Two cases of resistant gonorrhoea diagnosed in the UK.  GOV.UK.
  10. Public Health England (2020) TB Official Statistics UK: 2000 to 2019.
  11. Mulani, M. S. et al. (2019). Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review.   Front Microbiol, Vol 10,
  12. Decraene, V. et al. (2018). A Large, Refractory Nosocomial Outbreak of Klebsiella pneumoniae Carbapenemase-Producing Escherichia coli Demonstrates Carbapenemase Gene Outbreaks Involving Sink Sites Require Novel Approaches to Infection Control.   Antimicrob Agents Chemother, Vol 62,
  13. Lim, F. H. et al. (2020). An outbreak of two strains of OXA-48 producing Klebsiella pneumoniae in a teaching hospital.   Infection Prevention in Practice, Vol 2, 100033.
  14. TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY: FINAL REPORT AND RECOMMENDATIONS (2016).
  15. UK 5-year action plan for antimicrobial resistance 2019 to 2024.  GOV.UK.
  16. UK 20-year vision for antimicrobial resistance.  GOV.UK.
  17. UK 5 Year Antimicrobial Resistance Strategy 2013 to 2018.  GOV.UK.
  18. Reinvigorating our system for international health.  GOV.UK.
  19. It’s time to fix the antibiotic market.  Wellcome.
  20. Fund, A. A. The AMR Action Fund announces its first non-industry investments, raising an additional US$140 million toward addressing antimicrobial resistance (AMR). 
  21. Antimicrobial Resistance Research & Development.  AMR Action Fund.
  22. Mahase, E. (2020). UK launches subscription style model for antibiotics to encourage new development.   BMJ, Vol 369, m2468. British Medical Journal Publishing Group.
  23. Models for the evaluation and purchase of antimicrobials | Scientific advice | Life sciences | What we do | About.  NICE. NICE.
  24. NHS England » How the ‘NHS model’ to tackle antimicrobial resistance (AMR) can set a global standard.
  25. (Inter)nationalising the antibiotic research and development pipeline – The Lancet Infectious Diseases.
  26. Nesta [online] Challenge.   Longitude Prize. Accessed on 23/3/21
  27. Papkou, A. et al. (2020). Efflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates.   Nature Communications, Vol 11, 3970. Nature Publishing Group.
  28. A novel strategy for using compounds as ‘anti-evolution’ drugs to combat antibiotic resistance | University of Oxford.
  29. Artificial intelligence yields new antibiotic.  MIT News | Massachusetts Institute of Technology.
  30. Lv, J. et al. (2021). A review of artificial intelligence applications for antimicrobial resistance.   Biosafety and Health, Vol 3, 22–31.
  31. Hall, C. et al. (2021). Antimicrobial Resistance and Immunisation. 
  32. Tagliabue, A. et al. (2018). Changing Priorities in Vaccinology: Antibiotic Resistance Moving to the Top.   Front. Immunol., Vol 9, Frontiers.
  33. Ota, Y. et al. (2019). A rapid and simple detection method for phenotypic antimicrobial resistance in Escherichia coli by loop-mediated isothermal amplification.   J Med Microbiol, Vol 68, 169–177.
  34. Mutreja, A. et al. Antibiotic resistance: cheap diagnostic test could be a saviour.   The Conversation.
  35. Bonnet, M. et al. (2020). Bacterial culture through selective and non-selective conditions: the evolution of culture media in clinical microbiology.   New Microbes and New Infections, Vol 34, 100622.
  36. Collier, P. et al. (2018). Two years on: an update on achievement towards the recommendations of the antimicrobial resistance report.   Journal of Applied Microbiology, Vol 125, 308–312.
  37. AMRSim | Welcome. [online] Accessed 23/3/21
  38. PM confirms £3.7 billion for 40 hospitals in biggest hospital building programme in a generation.  GOV.UK.
  39. New leadership for construction of 40 new hospitals.  GOV.UK.
  40. How covid-19 is accelerating the threat of antimicrobial resistance | The BMJ.
  41. Kouassi, V. COVID-19 and antimicrobial resistance: Are there any unknowns that will become known? – by Stephan Harbarth.   REVIVE.
  42. Adler, H. et al. (2020). Low rate of bacterial co-infection in patients with COVID-19.   The Lancet Microbe, Vol 1, e62. Elsevier.
  43. Co-infections: potentially lethal and unexplored in COVID-19 – The Lancet Microbe.
  44. Clancy, C. J. et al. (2020). Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect?   Clinical Infectious Diseases, Vol 71, 2736–2743.
  45. Bengoechea, J. A. et al. (2020). SARS-CoV-2, bacterial co-infections, and AMR: the deadly trio in COVID-19?   EMBO Molecular Medicine, Vol 12, e12560. John Wiley & Sons, Ltd.
  46. Monnet, D. L. et al. (2020). Will coronavirus disease (COVID-19) have an impact on antimicrobial resistance?   Euro Surveill, Vol 25,
  47. Maillard, J.-Y. et al. (2020). Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A position paper.   Am J Infect Control, Vol 48, 1090–1099.
  48. Lu, J. et al. (2021). Disinfection spreads antimicrobial resistance.   Science, Vol 371, 474–474. American Association for the Advancement of Science.
  49. Kraemer, S. A. et al. (2019). Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy.   Microorganisms, Vol 7,
  50. Dowling, A. et al. (2021). Reservoirs of Antimicrobial Resistance. 
  51. Hirst, D. et al. (2021). Commons Library analysis of the Environment Bill 2019-20. 
  52. Interagency Coordination Group on Antimicrobial resistance (2019)No Time to Wait: Securing the future from drug-resistant infections.

Image: E. coli Bacteria by NIAID under CC BY 2.0, cropped

Related posts