Last week's World Antibiotic Awareness Week was aimed at continuing to raise the profile of importance of tackling antimicrobial resistance.1

Antimicrobial resistance (AMR) is becoming an increasingly serious threat. There are profound health and macroeconomic consequences for the world, especially in emerging economies, if antibiotic resistance is not combated effectively. The final report of the Review on Antimicrobial Resistance commission estimates that, if not addressed, by 2050 the consequences from losing the ability to treat infections effectively could kill 10 million people per year, leading to a higher mortality than cancer or road traffic accidents.2 This week's blog is by one of our colleagues, George Walker, and explores the causes and risks of antibiotic resistance and what actions can be taken to avoid the dawning of a 'post-antibiotic era' that would put the achievements of modern medicine at significant risk.

Antibiotics were discovered in the early 20th century as an effective treatment to the many bacterial infections, like bacterial pneumonia, wound infections and tuberculosis (TB) that were killing millions of people. They went on to revolutionise healthcare, becoming one of the greatest medical advances of the century. However, antibiotic resistance occurs naturally and the misuse of antibiotic prescribing has allowed bacterial pathogens to develop resistance to some of the most powerful drugs used to combat them. Additionally, the problem extends to all microbes that have the potential to mutate and render both known and newly developed drugs ineffective.3 The recent crisis of antimicrobial resistance has been exacerbated because the pace at which we are discovering new antibiotics has slowed drastically, whilst the use of antibiotics still continues to rise.4

Today even last-line antibiotics are starting to fail

The damaging effects of antibiotic resistance are already manifesting themselves across the world. Antimicrobial-resistant infections currently claim at least 50,000 lives each year across Europe and the US alone, with a total estimate of 700,000 annual deaths caused by AMR globally. However, reliable estimates of the true burden are scarce.5

Easily spread and broadly present multi-resistant 'superbugs' such as methicillin-resistant (MRSA) affect even previously healthy people, and can cause devastating diseases such as meningitis, pneumonia and sepsis.6 Evidence shows that across Europe 7 out of 30 countries reported percentages of resistance of above 25 per cent7. However, MRSA also serves as a good example how increasing awareness succeeded in inciting action, which has resulted in a significantly decreasing trend of resistance at EU/EEA level between 2012 and 2015. Strategies that helped to achieve this trend urgently need to inform the plans to combat the proliferation of other equally deadly antimicrobial-resistant bacteria.

Although in modern, well-funded healthcare systems, obtaining access to second and third-line treatments when first-line antibiotics fail, may often not be an issue, mortality rates for patients with infections caused by resistant bacteria are significantly higher, as are their costs of treatment. Moreover, even for last-line antibiotics under AMR surveillance, AMR continues to increase. For example, the average percentage of resistance in Klebsiella pneumoniae to the last-line treatment with carbapenem rose from 6.2 per cent in 2012 to 8.1 per cent in 20158 . As a result, we are seeing in parts of Europe an increasing number of patients in intensive care units, haematology units and transplant units who have pan-resistant infections, meaning there is no effective treatment available.9

The threat of increasingly drug-resistant infections is of even greater severity in developing countries. Emerging resistance to treatments for diseases, such as tuberculosis, have enormous economic and health impacts and pose an additional barrier for development. WHO estimates that, in 2014, there were about 480 000 new cases of multidrug-resistant tuberculosis (MDR-TB), a form of tuberculosis that is resistant to the 2 most powerful anti-TB drugs. Among new TB cases in 2014, an estimated 3.3% were multidrug-resistant.10

Evolving strategies to combat antimicrobial resistance

Awareness of the problem is growing and key stakeholders from governments, health organisations, and large corporations are recognising the need for action. Steps, already taken will need to be scaled up and accelerated.

  • Getting the policies right
    At a global level the WHO is helping countries develop their national action plans, and to build health and surveillance capability so that countries can manage antibiotic resistance properly. Collaborating on a global scale is what will truly help tackle the problem head on.

    As a result, many countries are beginning to stop the practice of using antibiotics for growth promotion in livestock. Countries such as Denmark, have successfully implemented strategies which drastically limit the use of antibiotics in livestock. These policies have resulted in significant declines in resistant microbes found within animals and meat, whilst additionally having little negative impact on the pork industry, in particular.11

    Finally, tackling drug resistance should be aligned with the growth objectives of low and middle-income economies. Sustained growth will be helped by investing in sanitation and basic health infrastructure that protect citizens from excessively high rates of infection, while at the same time addressing AMR.

  • Harnessing scientific advances for diagnostics, monitoring and surveillance
    Advances in genetics, genomics and computer science will likely change the way that infections and new types of resistance are diagnosed, detected and reported worldwide. For example, rapid DNA sequencing technology can enable us to directly draw links to outbreaks sources and track their spread. An approach which has been successfully piloted in a small project tracking foodborne illness. This surveillance of antibiotic resistance is key to prioritising action, so that we can fight back faster when bacteria evolve to resist drugs.12

    Likewise, extending the access to rapid point-of-care diagnostics is needed to enable clinicians to only prescribe antibiotics in the presence of a bacterial infection.13

  • Extending collaboration between pharmaceutical companies and the public sector
    Research and development of antimicrobial drugs has significant negative externalities, where the optimal clinical situation is being able to avoid the use of second- and third-line drugs. A 2015 report by the Review on Antimicrobial Resistance commission suggest new incentives and funding models to make antibiotics R&D commercially sustainable, that include lump-sum payments for successful drug development and a global AMR Innovation Fund. However, these interventions require political leadership at a global level. 14

    The pharmaceutical industry has started to recognise its role and in September 2016, 13 leading pharmaceutical companies came together to agree a comprehensive roadmap that lays out key commitments that the industry pledges to deliver by 2020 to reduce AMR. These include:
    • establishment of a common framework for manufacturing and supply chains to better manage antibiotic discharge
    • increased engagement in provider and patient education to reduce misuse and uncontrolled antibiotic purchase
    • improving global access to current and future antibiotics, vaccines and diagnostics
    • extending open collaborations between industry and the public sector to address R&D challenges related to new antibiotics, vaccines and diagnostics.15

  • Changing behaviours of all stakeholders to secure sustainable antibiotic treatments
    Addressing the present crisis above all requires behaviour change among all stakeholders. This includes clinicians, the agricultural industry and patients.

    Initiatives such as 'Antibiotic guardian' enable healthcare professionals and the public to make simple pledges how to make better use of antibiotics. These include:
    • not to demand antibiotics for common colds and self-limiting minor illnesses and only to use antibiotics when adequately prescribed by a healthcare professional, adhere to treatment advice and never to share or use leftover antibiotics and return unused antibiotics to pharmacy for safe disposal
    • following clinical guidance on prescription, making use of available material for patient education and adopting strategies such as the delayed prescription for infections that are likely to be self-limiting
    • adequately monitoring and sharing prescribing data and addressing variations against national and international averages.16

Effective antimicrobial drugs are a precious resource that cannot be taken for granted. It will require collaborative efforts of all to preserve the effectiveness of antibiotics, prevent the spread of infections and make sure, that patients all across the world have access to an effective treatment when needed.

Footnotes

1 http://www.who.int/campaigns/world-antibiotic-awareness-week/en/  
2 https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
3 https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf
4 http://ecdc.europa.eu/en/publications/_layouts/forms/Publication_DispForm.aspx?List=4f55ad51-4aed-4d32-b960-af70113dbb90&ID=1601
5 http://www.who.int/mediacentre/factsheets/fs194/en/
6 http://blogs.deloitte.co.uk/health/2016/09/the-uk-sepsis-trust-and-starfish-a-powerful-story-of-a-sepsis-survivor-why-raising-awareness-is-key-.html
7 http://ecdc.europa.eu/en/eaad/documents/antibiotics-resistance-eu-data-2013.pdf
8 http://crofsblogs.typepad.com/h5n1/antibiotic-resistance/
9 http://ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?ID=1510&List=8db7286c-fe2d-476c-9133-18ff4cb1b568&Source=http%3A%2F%2Fecdc%2Eeuropa%2Eeu%2Fen%2Fhealthtopics%2Fantimicrobial%2Dresistance%2Dand%2Dconsumption
%2Fantimicrobial%5Fresistance%2Fwhats%2Dnew%2FPages%2Fwhat%2Dis%2Dnew%2Easpx
10 https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
11 http://ehp.niehs.nih.gov/122-a160/
12 https://directorsblog.nih.gov/2014/09/18/new-strategies-in-battle-against-antibiotic-resistance/
13 http://blogs.deloitte.co.uk/health/2016/01/can-new-diagnostic-tests-tackle-antibiotic-resistance.html
14 https://amr-review.org/sites/default/files/SECURING%20NEW%20DRUGS%20FOR%20FUTURE%20GENERATIONS%20FINAL%20WEB_0.pdf
15 http://www.ifpma.org/wp-content/uploads/2016/09/AMR-Roadmap-Press-Release_FINAL.pdf
16 http://antibioticguardian.com/

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