Antimicrobial Resistance - Q4 2021 by Mediaplanet UK&IE

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Antimicrobial Resistance Dr Amina Abubakar Bello & Nurse Dorcas Samuel Dr Amina Abubakar Bello disinfects her hands as nurse Dorcas Samuel prepares her to go into the theatre for a surgery in the Jummai Babangida Aliyu Maternal and Neonatal Hospital (JBAMN) in Niger State on 24 February 2021. © WHO / Blink Media - Etinosa Yvonne | WHO have approved use of front-cover image

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Menarini is committed to the global fight against antimicrobial resistance by: Supporting the appropriate use of antibiotics Collaborating strategically with others to find practical and long-term solutions to antibiotic resistance

Email: antibiotics@menariniuk.com Prepared: November 2021 / PP-AI-UK-0237

Developing the economic case for AMR There is currently an inadequate economic case for galvanising AMR financing. Current knowledge should be used to develop models to advocate for urgency of action and investment in AMR.

F Dr Haileyesus Getahun Director, Department of Global Coordination and Partnership, and Joint Tripartite Secretariat on Antimicrobial Resistance, World Health Organization

inancing for the global response to antimicrobial resistance (AMR) is insufficient. In 2020, only one in five countries reported funding sources for their national action plans on AMR and only USD 1.6 billion was invested in research and development across humans, animals, plants and the environment. In comparison, global military expenditure in 2020 was USD 1981 billion. At the same time, existing estimates of the costs of AMR containment measures are not robust, ranging from USD 4-9 billion annually, far less than the estimated annual needs of USD 26 billion and USD 15 billion for HIV and TB respectively. There is also no compelling economic case on the return on investment in AMR such as for universal access to contraception (every US dollar spent yields USD 120 in return) or increasing tobacco prices (USD 22 return per dollar invested). Current

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estimates of the global economic loss due to AMR are futuristic and do not account for the short- and medium-term costs of inaction. More reliable data is required These challenges are due to inadequate systems to create and collect reliable data. Better costbenefit and return on investment estimates are critical to galvanise financing for the response to AMR globally and in countries. Current and annual economic impacts of AMR also need to be assessed. While establishing systems to collect robust data, the current knowledge base - including expert opinion - should be used to develop models for generating information to advocate for more urgent action and investment in AMR. The potential efficiency gains across humans, animals, plants and the environment may be particularly compelling from an economic perspective due to the benefits of multisectoral action.

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Urgent need for tangible action AMR has been mentioned consistently in recent G7 and G20 declarations, including the leaders’ declarations and communiqués of ministers of health, agriculture, environment and finance. However, the commitments made to date lack tangible and specific actions. All countries should respond to the looming crises of AMR through the implementation of ambitious, multisectoral national action plans across the One Health spectrum and allocate adequate and sustainable domestic financing for the response in national plans and budgets. G7 and G20 countries must also play a more ambitious and active leadership role, including by availing external resources and increasing incentives for research and development on AMR.

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MICROBIOLOGY Challenges and opportunities in antimicrobial research.

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Professor Stephen Baker Director of Research (medicine), University of Cambridge and Chair of the ‘A Sustainable Future’ Steering Group World antibiotics awareness_v2.indd 1

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Joining forces against AMR: A ‘Manhattan Project’ for good Paid for by Novartis

Image provided by Sandoz: A birds eye view of the Kundl antibiotics plant in Austria

We have to get away from the simplistic belief that R&D will produce a ‘silver bullet’ to magically end AMR, because every new drug will in time also be subject to resistance.

COVID-19 has highlighted how vulnerable we still are to infectious diseases. Antimicrobial resistance, often dubbed the “silent pandemic”, threatens to undermine the efficacy of common antibiotics, the foundation of modern healthcare.

T Sonita ChadaGrathwol, Ph.D Sr. Program Manager, Anti-microbial Resistance (AMR), Novartis

Dr Dominic De Souza Global Head Anti-Infectives Sustainability and AMR Program, Sandoz

he history of medicine, says Dominic De Souza, Global Head Anti-Infectives Sustainability and AMR Program at Sandoz, can be divided effectively into two stages: before and since antibiotics. Before the discovery of penicillin in 1928, even a minor infection could prove deadly. De Souza says: “Penicillin, and antibiotics generally, transformed healthcare; think of tuberculosis, where the effective first-line treatment used to be a combination of fresh air and sunlight! “Antibiotics today save and protect millions of lives: by treating infectious diseases and by enabling countless routine surgeries or treatments where you temporarily suppress the immune system, including chemotherapy.” The weakest bear the brunt AMR, which occurs when microorganisms evolve to resist antimicrobial medicines, represents a unique and growing threat to the sustainable use of antibiotics. A natural phenomenon, it has been progressively accelerated by antibiotic (mis)use over the decades. The result, as called out by the

2016 UK O’Neill report, is that an estimated 700,000 people now die every year due to AMR. What’s more, as Sonita ChadaGrathwol, Program Lead for the cross-divisional Novartis AMR Program, says: “Children, the elderly, women and the poorest of the poor bear the brunt.” She adds: “According to leading NGO GARDP, 214,000 babies die every year from drug-resistant infections – that’s nearly a third of the total annual death toll. Of five million-plus annual underfive deaths, they estimate that three million are due to infectious diseases such as pneumonia and sepsis, with up to 40% now resistant to standard treatments.” While AMR is more common in developing nations, drug-resistant bacteria can infect anyone, anywhere. As COVID-19 has shown, treatment-resistant pathogens can spread rapidly and uncontrollably worldwide. A balanced global approach De Souza warns that AMR cannot be simply eliminated, but he is hopeful that its impact can be minimised by a “truly holistic approach” – if we act now.

“We need to focus equally on all four pillars of the AMR response strategy – as well as innovation, that means responsible manufacturing, responsible use and appropriate access.” Responsible manufacturing means minimising antibiotic residues in all production-related waste streams, proper use of resources, optimal hygiene and safe waste disposal throughout the value chain. De Souza notes that Sandoz, a leading global supplier of generic antibiotics and the only remaining company with a vertically integrated antibiotics supply chain based in Europe, is now celebrating 75 years of penicillin production at Kundl in Austria. Indeed, it is investing more than EUR 150 million into its Kundl-based production network. Responsible use means appropriate education to prevent overuse, underuse or misuse of existing antibiotics. Diagnostics and surveillance also help to radically improve point-of-care decisions. It means working with partners to drive stewardship, both on internally-led programs such as Novartis Healthy Family and on external programs, for instance with the Commonwealth Pharmacists Association (CPA) and the Ecumenical Pharmaceutical Network (EPN). Appropriate access is about getting the right drug to the right patient at the right time. This means both preventing millions of avoidable deaths due to lack of antibiotics and preventing the spread of AMR due to lack of appropriate treatments. Healthcare is not a cost Chada-Grathwol believes that lasting success will need a wide-ranging public-private collaboration effort. The global initiative to develop a COVID-19 vaccine in record time shows how success might look, while the patchy progress towards equitable global distribution shows what could go wrong. She concludes: “We need to change the political discourse so that spending to ensure global public health is seen as an investment, not a cost. Think of this as a ‘Manhattan Project’ for the public good.”

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Diagnostic tests are vital in the fight against antimicrobial resistance The COVID-19 pandemic has focussed the world’s attention on the role and importance of diagnostic testing.

iagnostic tests provide essential data to support treatment decisions; 70% of patient information comes from diagnostic tests. Many tests are done in hospital laboratories, but increasingly technological improvements are enabling access to tests outside traditional settings.

Doris-Ann Williams MBE Chief Executive, British In Vitro Diagnostics Association

Keeping the focus on the AMR crisis Diagnostic testing is also critical to managing antimicrobial resistance (AMR). During this year, AMR, like so many other healthcare issues and diseases, has been overlooked while the global population struggles with the COVID-19 pandemic. Yet, AMR remains a global health disaster that is already killing 700,000 people a year. It is predicted to cause 10 million deaths each year by 2050 if the current situation is not improved. Hence it is vital to remember that this huge threat to public health has not gone away. We need to reduce the inappropriate use of both antibiotics and antimicrobials, to ensure they remain active against pathogens when needed most.

admissions with influenza or pneumonia. Tests can distinguish between a bacterial or viral infection, allowing their symptoms to be treated most appropriately. Critically ill patients with suspected infection need to be tested to diagnose the underlying pathogen, or alternatively to rule-out sepsis, which can rapidly become fatal or leave people with life changing damage. Furthermore, with COVID-19, almost all patients admitted to hospital are given a five-day course of empiric antibiotics despite the low incidence of bacterial superinfections. Using diagnostic tests gives clinicians confidence to stop inappropriate antibiotics much earlier, helping the fight against AMR. Diagnostic tests provide critical pieces of information to support patient treatments and to monitor if treatments are effective. While the tests can seem simple, there is an entire segment of the life sciences industry concentrating on developing and manufacturing these tools and the equipment required to perform them using the latest biotechnology. These are the weapons we need to deploy on the frontline in this ongoing battle against AMR.

Helping to diagnose patients more efficiently Diagnostic testing can play a key role in antibiotic stewardship. For example; managing winter hospital

Developing new antibiotics – the next great challenge

2021 AMR Preparedness Index discovered that, overall, countries’ performance was the weakest in this category.3

For a long time, the world has recognised the threat posed by antimicrobial resistance (AMR) but the pipeline of new antibiotics to tackle it remains too weak.

he WHO has recognised AMR as one of the urgent health challenges of the decade.1 But, while we have seen progress in tackling this looming catastrophe in some areas, there is one that remains woefully unaddressed – enabling the development of new antibiotics. Research and development for AMR There is growing consensus that we need to address the unique market dynamics of antibiotics, where new ones are only used in the direst of needs, in order to attract investment into R&D and build a pipeline. The solution includes new pull incentives,

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rewarding successful development and rebuilding investor confidence, as well as changing how we value antibiotics and how we pay for them.2 Antibiotics do much more than prevent individual infections – they are critical enablers of many routine procedures and treatments through pre-emptive use or as accompanying therapy. The 2015 WHO Global Action Plan on AMR includes as one of the five objectives the need to develop an economic case for sustainable AMR R&D investment. While many reports in recent years have demonstrated the need for policy reforms in the space, progress has been slow. Unsurprisingly, the

Leading by example Thankfully, some leading countries are stepping up. The draft US PASTEUR Act proposes a broad reward range for new antibiotics that would address public health needs. Non-private procurement would proceed through a subscription model, whereby a fixed fee is paid to access as much antibiotic as is reasonably needed by the health system. The UK has shown good leadership on AMR under their G7 presidency this year and is piloting a novel subscription model that considers additional value elements and has the potential to help reinvigorate the pipeline – but only if all leading countries follow suit. There is only so much time left. In 2020, the biopharmaceutical industry stepped up and created the AMR Action Fund, a USD 1 billion breakthrough initiative to bridge the funding gap. But policy makers and governments need to act too. Now.

James Anderson Executive Director, Global Health, IFPMA

References 1. https://www.who.int/news-room/photo-story/ photo-story-detail/urgent-health-challenges-forthe-next-decade 2. https://www.ifpma.org/resource-centre/globalprinciples-on-incentivizing-antibiotic-rd/ 3.https://globalcoalitiononaging.com/ initiatives/#initiative-2076

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Aleks Engel Partner, Novo Holdings and Director, REPAIR Impact Fund

The demise of antibiotics has been greatly exaggerated

Over the last 10 years, investors and big pharma have abandoned the field of antibiotic development because newly launched products generated poor revenues compared to other fields, such as oncology. Now is the time to re-enter.

he first principle of biopharmaceutical investors is to identify a match between innovation and unmet need. However, with about 200 approved antibiotics in 20 different drug classes, many needs were addressed for a while. Antimicrobial resistance (AMR) has slowly rendered older product classes obsolete, but with a combination of products that had become generic and thus cheap, infectious disease doctors had many available treatments at hand. Today, new products are rarely used (also due to good stewardship to minimise new resistance development) and small companies manufacturing new products, such as Achaogen and Melinta, have gone bankrupt. The onslaught of AMR has, however, continued and we now have close to a million deaths from drug-resistant infections per year, a number which keeps rising. Increasingly, older antibiotics have become inadequate, even in combinations. One new product, ceftazidime/ avibactam, designed to circumvent certain bacterial resistance defences is selling greater than USD 500 million on a yearly runrate1 and is on track to becoming the next antibiotic blockbuster. This is the data point that sceptical

investors have been waiting for – proof that it is possible to make money with a differentiated product. Another way to circumvent resistance is with the use of vaccines, avoiding the infection altogether. Vaccines (also against bacterial infections) are beginning to attract investors again. A good example was the EUR 47 million (USD 57 million) Series B investment in Minervax developing a vaccine against Strep B. A good time to invest in innovation The good news for investors considering stepping back into anti-infectives is that innovation is high. A recent pipeline review published in Nature2 found more than 400 early stage (pre-clinical) programs targeting high priority resistant pathogens. There are plenty of investment opportunities and the world is in dire need of these innovations becoming actual drugs that will save lives.

Drug stewardship receives a boost from improved diagnostics Innovations in multiplex PCR diagnostics are poised to help healthcare professionals prescribe more targeted therapies for patients – improving outcomes and combatting antibiotic resistance in the process. Keith Stanley Professor at the University of New South Wales and Managing Director, AusDiagnostics WRITTEN BY Kate Sharma

The need for improved diagnostics Efforts to bring new drugs to market remains slow, so good stewardship of those antibiotics still fit for purpose is vital. However, a lack of diagnostic information makes it hard for healthcare professionals to make the best choices. Empirical therapy is based on experience, not diagnostics, many doctors prescribe the latest drugs as a ‘catch all’ because they simply have no way of knowing whether their patients have resistant strains or not. This poses several problems. While the latest drugs may treat the infection, they aren’t necessarily as effective in patients who have wild-type strains. They’re also often not tolerated as well, and their over-use will inevitably lead to further resistance rendering the drug useless over time.

References 1. Based on L3M extrapolated from latest data ending June of 2021. Source: IQVIA 2. https://www.nature.com/articles/s41579-0190288-0

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utating bacteria continue to outwit us, with drug-resistant strains killing more than 700,000 people each year. The United Nations interagency group on antimicrobial resistance believe things will get worse, estimating that the figure could rise to 10 million a year by 2050 - double the number of people who have died globally from COVID-19.

Multiplex PCR diagnostics Keith Stanley, Professor at the University of New South Wales and Founder and Managing Director at AusDiagnostics, is hopeful that Multiplex-Tandem PCR, which can measure up to 24 different targets, will give doctors the insight to prescribe treatment much more accurately. Molecular diagnostics typically test for organisms and resistant genes that are ‘present’, but there is also the scope to test for what is ‘absent’. This could be game changing when diagnosing and treating complex infections where gram-negative bacteria with numerous resistant genes may be involved. As Stanley points out, improved diagnostics empower healthcare professionals to make the best decision for their patients while also considering the global, longterm impact of the drugs they prescribe. He confirms, “We made a 16-target test that enabled doctors to prescribe with 90% effectiveness. With a 24-target test, we are confident we can get this to 95% or even higher.”

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Developing a strategy to improve antimicrobial prescribing

neuro-rehabilitation patients may appear clinically well but microbiology results show a heavy growth of microorganisms. The Infection Prevention and Control (IPC), respiratory, tissue viability and continence CNSs focus on conservative management of symptoms before antimicrobial treatment is considered.

ollowing the UK FiveYear AMR Strategy, the ICT, as the antimicrobial stewardship guardian for the hospital, carried out an extensive audit of antimicrobial prescribing practice. The audit showed the need for a standardised assessment process and provision of an antimicrobial formulary which was used under two different care models within the hospital: long term care (LTC) led by general practitioners (GPs) and brain injury services led by neuro-rehabilitation consultants. The guiding principle was to ‘start smart - then focus’. The ICT audit (2014 - 2015) showed the need for improvement in the following areas: • Management of clinical

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The Infection Control Team (ICT) led a multidisciplinary approach to antimicrobial stewardship which improved the quality of antimicrobial prescribing used under two different models of care within the hospital.

symptoms (i.e. improving aseptic technique for wound, respiratory and continence care). • Appropriate antimicrobial prescribing. • Collaboration within the multi-disciplinary team (MDT). The clinical nurse specialists (CNS) role in AMR With regard to symptoms of infection, LTC patients have a different clinical presentation compared to neuro-rehabilitation patients. For example, increased chest secretions or a chronic wound in the LTC patient may not be an indicator of infection, but rather that their postural management needs reviewing. On the other hand,

Multidisciplinary team approach Understanding the complexity of antimicrobial resistance is essential. The ICT recognised the importance of using a MDT approach and working towards a common goal – that is patient safety through the reduction and prevention of antimicrobial resistance. The ICT, medical team, pharmacist, CNS team and physiotherapists worked closely to assess patients, review care plans and send specimens for culture and sensitivities prior to appropriate antimicrobial prescribing.

Mona Liza Marinas Clinical Nurse Specialist for Infection Prevention and Control / Antimicrobial Stewardship Lead Nurse, Royal Hospital for Neurodisability London, United Kingdom

Antimicrobial formulary within the prescribing policy In February 2015, the first antimicrobial formulary was developed for use across the entire hospital as part of the antibiotic prescribing policy. Standardisation of practice enhanced antimicrobial stewardship and ensured the timely review of antibiotic use for all patients.

The vital role of nurses and midwives in the management of AMR The World Health Organization is calling for investment in the health workforce to ensure patients receive safe and high-quality, evidence-based care.

N Dr Emily McWhirter Nurse Consultant, World Health Organization

urses and midwives in health care settings around the world are responsible for the safe administration of medicines to patients. They are also responsible for monitoring patients’ wellbeing, vital signs and changes in clinical condition. To provide high-quality, evidence-based and safe patient care, nurses must have up-to-date knowledge of the issues surrounding antimicrobial resistance (AMR) and must take action to address this global health threat. AMR and the risks it poses to global health should be part of all nurse pre-service training curricula and embedded into in-service training and development programmes at all stages - from student nurse or midwife to senior nurse or midwife leader. Nurses and midwives as leaders Nurses and midwives must be empowered to work alongside doctors, pharmacists and all members of the multi-disciplinary team involved in the planning of a patients’ clinical care in order to ensure that patients receive appropriate, timely and needed antimicrobial treatment. They play a critical role in the development of guidelines for standardised assessment processes and by working with colleagues across all clinical disciplines are essential to co-ordinate and lead on data collection, monitoring and best practice initiatives. Investment in a well-trained health workforce Nurses and midwives are able to lead programmes of change within their own working environment in order

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to provide policies and protocols for safe medicines management. WHO Global Strategic Directions for Nursing and Midwifery, 2021-2025, endorsed at the 74th World Health Assembly in May 2021, promotes investment in leadership skills development for midwives and nurses, highlights policy actions urgently needed to establish and strengthen senior leadership positions for nursing and midwifery, workforce governance and management as well as contributing to health policy formulation. Nurses and midwives are well placed to be responsible for successful quality improvement programmes to establish local guidance for safe antimicrobial prescribing practice. Opportunities exist for nurses to take on advanced roles becoming clinical specialists, lead teams and supervise and mentor within their workplace. Senior nursing and midwifery leaders should encourage and ensure nurses and midwives can develop competencies in speciality areas and become experts in advanced practice. Globally, WHO is calling for countries to invest in their health workforce to ensure that patients receive safe, high-quality, evidence-based and timely care where and when they need it.

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Wound care management: assess sooner, act faster and address earlier Antimicrobial stewardship is a critical factor within effective wound care. It ensures that antimicrobials are used efficiently and appropriately, with the right product delivered to the right patient at the right time to support good clinical outcomes and avoid the spread of infection. WRITTEN BY Mark Nicholls

Education to deliver appropriate intervention

ducation, effective tools and infection management (IM) pathways are crucial in supporting diagnosis of infection and delivering appropriate intervention with topical antimicrobial dressings, according to Dr Kevin Woo, Full Professor at Queen’s University, School of Nursing and School of Rehabilitation in Kingston, Canada.

Education, effective tools and infection management pathways are crucial in supporting diagnosis of infection and delivering appropriate intervention with topical antimicrobial dressings. A further challenge with diagnosis and treatment of local infection and biofilm is in differentiating inflammation – which may be due to trauma and underlying pathology - from infection. Guidelines can help to deliver “the right product,

right patient, right time approach” in wounds, but he stresses that the IM pathway was important as it can prompt “consistency in care and confidence in decision-making.” As an evidence-based, clinically-oriented and user-friendly tool for translating knowledge to the bedside, the IM pathway has been validated and evaluated (See QR Code) in practice and will help bedside clinicians to identify signs associated with local biofilm infection. Dr Woo believes educating care teams and implementing the IM pathway in wound care is an important step and can be achieved with pocket-size tools to take to the bedside for wound assessment, supported by clinical expertise.

Dr Kevin Woo, PhD, RN, NSWOC, WOCC(C) Full Professor, Queen’s University

Challenges in treating biofilms

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linicians need to be aware of the challenges in treating biofilms; the importance of education to support diagnosis of infection and appropriate intervention; and the expertise for care of burn wounds, which are particularly prone to infection. Biofilms, a cluster of microbial cells imbedded in a matrix, can be particularly difficult to treat as the wound microenvironment can play a large part in shaping bacterial behaviour. However, Dr Matthew Malone, Director of Research at the South West Sydney Limb Preservation and Wound Research Academic Unit in Australia, warns that biofilms are not visible to the naked eye and are heterogeneously distributed in tissue, making it difficult to diagnose or target them.

Inappropriate antimicrobial treatment in a wound compromised by biofilm can lead to chronic infections. “In some chronic biofilm infections, biofilm dispersal or social interactions may lead to acute infection flairs requiring more urgent interventions,” he adds. “Managing wound biofilms requires a multifaceted approach. This includes addressing underlying patient factors in addition to physically removing infected tissue through debridement. Antimicrobials also have a role to play, however clinicians must select agents which demonstrate anti-biofilm activity.” “Only when clinicians understand that the problem in front of them is driven by biofilm can they make decisions on antimicrobials which are evidencedbased,” says Professor Malone.

Dr Matthew Malone, PhD Director of Research, South West Sydney Limb Preservation and Wound Research Academic Unit

Reducing infection risk in wound care

urn wounds are particularly prone to infection, primarily due to loss of the mechanical barrier of the skin and the immune-compromising consequences of burns.1 Dr Emma Woodmansey, Clinical Strategy Director, Advanced Wound Care at Smith and Nephew, says this can lead to significant morbidity and mortality, with up to 75% of burn victim deaths associated with wound infection.2 In addition, prolonged hospital stays also increase the risk of developing an infection caused by multidrug resistant organisms.3 “This high risk of infection in burn wounds can lead to the use of antibiotics prophylactically to prevent infection developing,” she continues. “However, every

time an antibiotic is used, the chance of resistant organisms developing is increased.”4,5 Antimicrobial dressings, such as silver dressings, can help prevent the spread of resistant bacteria from wounds to other patients in burn units.6 “Effective silver dressings have been shown to rapidly kill bacteria, even those resistant to many different antibiotics,” she adds. In daily practice in burn care silver dressings have been shown to decrease infections, antibiotic use, and length of stay, therefore minimising progression to systemic infection and sepsis, thus reducing the human and economic burden of burn wound management.6

Emma Woodmansey, PhD Clinical Strategy Director, Advanced Wound Care, Clinical and Medical Affairs, Smith and Nephew

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References 1. Church, D., Elsayed, S., Reid, O., Winston, B. & Lindsay, R. Burn wound infections. Clin. Microbiol. Rev. 19, 403–434 (2006), 2. Ansermino, M. & Hemsley, C. Intensive care management and control of infection. BMJ 329, 220–3 (2004), 3. Chen, Y. Y. et al. Trends in microbial profile of burn patients following an event of dust explosion at a tertiary medical center. BMC Infect. Dis. 20, 1–11 (2020), 4. ISBI Practice Guidelines Committee, Steering Subcommittee & Advisory Subcommittee. ISBI Practice Guidelines for Burn Care. Burns 42, 953–1021 (2016), 5. Palmieri, T. & ISBI Practice Guidelines Committee. ISBI Practice Guidelines for Burn Care, Part 2. Burns 1–90 (2018), 6. Woodmansey, E. J. & Roberts, C. D. Appropriate use of dressings containing nanocrystalline silver to support antimicrobial stewardship in wounds. Int. Wound J. 15, 1025–1032 (2018).

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Increasing pharmacists’ leadership skills through antimicrobial stewardship Leadership is a key skill required of pharmacists across all sectors of care and in tackling AMR, highlighting the critical role that pharmacy leadership can have on effective antimicrobial stewardship (AMS).

The overuse of antibiotics is one of the biggest threats to health care

eadership development and AMS feature as two of the 21 development goals of the International Pharmaceutical Federation. In addition, frameworks to support leadership development for pharmacists are available in the UK. However, there are few opportunities available for pharmacists to develop and demonstrate these skills. It has previously been reported that NHS staff participating in international health projects develop leadership skills essential for influencing change and developing new ways of working. The Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme* was first of its kind to mandate that pharmacists be included as essential members of each international partnership, in both UK and African teams. Developing leadership skills through global health fellowship The Chief Pharmaceutical Officers Global Health (CPhOGH) Fellowship was developed by Commonwealth Pharmacists Association (CPA) and Health Education England for UK pharmacists who were part of CwPAMS.1 Post fellowship year, all Fellows indicated that the skills and knowledge gained during the year were useful and applicable to their positions in the UK; 7/16 reported a change in job role, five received promotion and 10 started managing new aspects of services since commencing on their global health and fellowship year. A scoping report led by CPA, based on 484 survey responses and focus groups of 40 members across eight African countries, reinforced the need for a similar AMS leadership programme for pharmacists in Africa. Bi-directional learning was also a key component of CwPAMS. When the UK became a resource-limited setting for alcohol hand rub at the start of the COVID-19 pandemic, the UK team were able to locally produce WHO-formula alcohol hand rub after learning from colleagues in Zambia. *CwPAMS managed by CPA and THET is funded by UK aid Fleming Fund. References [1] Brandish, C.; Garraghan, F.; Ng, B.Y.; Russell-Hobbs, K.; Olaoye, O.; Ashiru-Oredope, D. Assessing the Impact of a Global Health Fellowship on Pharmacists’ Leadership Skills and Consideration of Benefits to the National Health Service (NHS) in the United Kingdom. Healthcare 2021, 9, 890. https://doi.org/10.3390/healthcare9070890

Dr Diane Ashiru-Oredope Global AMR Lead, Commonwealth Pharmacists Association

Victoria Rutter Executive Director, Commonwealth Pharmacists Association

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In health care, antibiotics are one of the most powerful drugs for fighting life-threatening bacterial or fungal infections. However, too many antibiotics are being used unnecessarily and misused, which threatens the usefulness of these important drugs.

ntibiotic resistance is one of the greatest public health challenges of our time as there are limited treatment options available for people infected with antibiotic-resistant bacteria or fungi. Antibiotic resistance jeopardises advancements in modern health care that we have come to rely on, such as joint replacements, organ transplants and cancer therapy. These procedures and treatments have a significant risk of infection and patients won’t be able to receive them if effective antibiotics are not available. What causes antibiotic resistance? Antibiotic resistance happens when the germs no longer respond to the antibiotics designed to kill them. That means the germs are not killed and continue to grow. It does not mean our body is resistant to antibiotics. Bacteria and fungi are constantly finding new ways to avoid the effects of the antibiotics used to treat the infections they cause. Infections caused by antibiotic-resistant germs are difficult, and sometimes, impossible to treat. Antibiotic resistance occurs naturally and is not a new problem. In fact, in 1942, one year after penicillin was introduced, resistant Staphylococcus aureus, Streptococcus pneumoniae and gonorrhea were reported. But antibiotic resistance is accelerated when germs are exposed to antibiotics and when those germs spread. Therefore, antibiotics should be used only when necessary and only for appropriate durations. Antibiotic use during the pandemic Antibiotics are not effective against COVID-19, because antibiotics do not treat infections caused by viruses. Antibiotic use varied across healthcare settings during the pandemic: • In hospitals, antibiotic use increased for some specific antibiotics like azithromycin and ceftriaxone, which are often used to treat community-onset respiratory infections. This use likely reflects difficulties in distinguishing COVID-19 from community-acquired pneumonia caused by bacteria when patients first arrive for inpatient healthcare. • In outpatient settings, such as doctor’s offices, antibiotic use has dropped significantly. This is likely because outpatient healthcare use declined during the pandemic. Azithromycin prescribing was higher than expected, especially in geographic areas with high

numbers of COVID-19 cases. This might be a reflection of its early promotion as a potential therapy, despite its ineffectiveness against viruses. • In nursing homes, antibiotic use spiked with changes in the pandemic, but remains lower overall compared to pre-pandemic measurements. In nursing home settings, azithromycin prescribing remained elevated through October 2020. Another way to improve antibiotic use is through vaccination. Vaccines are one tool to improve antibiotic use and prevent infections, including resistant infections. Getting vaccinated for illnesses like COVID-19 and the flu helps prevent hospitalisations and secondary bacterial infections, reducing antibiotic treatment. How to help reduce the threat of antibiotic resistance Protect yourself and patients from antibiotic resistance: • Prescribe antibiotics following clinical and treatment guidelines. • Use diagnostic tests (when available) to guide antibiotic therapy, including correct drug, dose, and duration. • Keep your hands clean by handwashing or using hand sanitizer. • Follow infection prevention and control guidelines. • Educate patients on when antibiotics are and are not needed. • Get recommended vaccines and encourage patients to do so, too. Appropriate antibiotic use helps fight antibiotic resistance and ensures these lifesaving drugs will be available for future generations. Everyone has a role to play. For more information, visit: cdc.gov/drugresistance/protecting_patients.html cdc.gov/drugresistance/covid19.html cdc.gov/antibiotic-use/antibiotic-resistance.html cdc.gov/antibiotic-use/q-a.html

Lauri A. Hicks, DO Director, Office of Antibiotic Stewardship, Centers for Disease Control and Prevention

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The crucial role of diagnostics to improve antimicrobial stewardship

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disciplines is still needed to leverage integrated solutions to their full potential. The next step to improving stewardship will be increasing visibility to the power of data and analytics by connecting diagnostic data and clinicians through clinical decision support software.

As one of the top 10 threats to human health, antimicrobial resistance (AMR) should not be underestimated. The World Health Organization estimates that 700,000 people die every year from antimicrobial resistant infections.

WRITTEN BY Mark Nicholls

References 1. World Health Organization, Coronavirus (COVID-19) Dashboard https://covid19.who.int/ 2. Forsman R. W. (1996). Why is the laboratory an afterthought for managed care organizations? Clinical chemistry, 42(5), 813–816. 3. Bradley J. Langford, et al., Bacterial co-infection and secondary infection in patients with covid-19: a living rapid review and meta-analysis, clinical microbiology and infection, Volume 26, Issue 12, 2020, Pages 1622-1629, ISSN 1198-743X, https://doi.org/10.1016/j.cmi.2020.07.016.

Find out more at go.biomerieux .com/optimize mydiagnostics

Figure 1. Role of diagnostics to support responsible antibiotic prescribing Adapted from Messacar et al. Journal of Clinical Microbiology 2017;55:715-723

The right antibiotic for the right indication at the right dose and duration. Diagnosis & treatment

Rapid diagnostic test results reported

Antimicrobial stewardship

Diagnostics are key Diagnostics support the goals of stewardship by ensuring the right antimicrobial for the right patient at the right time and in the right dose for the right duration. Optimised use of diagnostics for antimicrobial stewardship includes more rapid identification of pathogens, differentiating between bacterial and viral infections and supporting better clinical decision making with knowledge of antimicrobial susceptibility. Diagnostics provide critical surveillance data for assessing the status of AMR in a community, country or region. “In general, diagnostics in medicine have always been undervalued and it has been said that 70% of medical decisions are based on some type of diagnostic information, but only 3% of healthcare costs are spent on diagnostics.2” Diagnostics are emerging as one of the key tools for stewardship but collaboration across multiple

Mark Miller MD, FRCP(C) Executive VicePresident, Chief Medical Officer, bioMérieux

Patient

Lab

Increasing AMR education and stewardship Dr Mark Miller, who is Executive Vice-President and Chief Medical Officer at in-vitro diagnostics company bioMérieux, says within a hospital setting implementing successful stewardship requires three core components: sufficient budget, knowledgeable people, and the support from multidisciplinary staff, including the c-suite. In practice, however, he notes that stewardship implementation can vary between regions. Too often, communities may not know the severity of local AMR due to poor surveillance or

reluctance to share their data. While the goal of stewardship remains the same regardless of region, the lack of awareness and education for the behaviours contributing to AMR, regional impact, and the urgency of addressing the problem lends itself to many being “not convinced they have an AMR problem”. Dr Miller reminds us that “if we let it go on, it’s going to destroy us economically and medically.”

COVID-19 and the future of diagnostics The COVID-19 crisis has accelerated the issue of AMR and the full extent of the impending devastation caused by antibiotic overuse during the pandemic is not yet fully known. “All you have to do is look at statistics of the amount of antibiotics that are used because of COVID-19 to know that we are just a dynamite keg ready to explode. Essentially three quarters of patients in hospitals are getting broad spectrum antibiotics even though they come in with a pure diagnosis of COVID-19,” he says.3 Health systems are anticipated to return focus to AMR, including monitoring that had been paused. Optimised use of diagnostics will be critical to reduce the spread of multi-drug resistant infections in the healthcare setting, where antibiotics have been in highest use during the pandemic. “People do not grasp that if we do not control AMR, there will be no elective surgeries, chemotherapy, radiotherapy or all the procedures that we consider today to be low risk because associated infection risks will be too high.” Dr Miller concludes: “Remember how important COVID-19 diagnostics were in the first year of the pandemic, AMR-related diagnostics are going to be equally as important as we continue to battle this global health threat.”

ntibiotics have only been available to patients since the 1920s, with the discovery of penicillin. If we fail to act soon, the effects of antimicrobial (including antibiotic) misuse will be irreparable in as little as 29 years. The 2016 report chaired by economist Jim O’Neill predicts that AMR will cause 10 million deaths per year and cost the global economy USD 100 trillion. For comparison, the COVID-19 virus has resulted in an estimated 5 million deaths worldwide since the beginning of the pandemic as of October 2021.1 This report has helped persuade healthcare stakeholders to take AMR more seriously and invest in better solutions for antimicrobial stewardship.

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Clinician

Microbiologist Diagnostic stewardship

Clinical evaluation

Rapid diagnostic test (RDT) ordered

The right test for the right patient at the right time.

Figure 2. How Rapid Diagnostics Optimize Treatment Adapted from O’Neill et al. The Review on Antimicrobial Resistance. 2015

Sick patient

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Figure 3. The “Optimal Equation” for appropriate antimicrobial prescribing Source: bioMérieux

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Appropriate sampling

Global not-for-profit partnerships must be part of drug resistance solution COVID-19 has made it clear our health and wellbeing are inextricably linked regardless of where we live. It has also demonstrated that unlocking global cooperation and investment cannot wait for a threat to emerge.

U Dr Manica Balasegaram Executive Director, Global Antibiotic Research and Development Partnership

nlike the novel coronavirus, which required bold, reactive efforts to identify medical countermeasures, there are too few promising solutions in the antibiotic pipeline. WHO warned in its ‘Antibacterial Pipeline Report’ that the drug development landscape was insufficient to address drug resistance. This is due to several factors, including the lack of profitability for developing new antibiotics. Commercial constraints discouraged private investment in preparing for pandemic threats. Tackling the threat of drug-resistant infections requires proactive funding and global cooperation within a One Health framework. Comprehensive approaches and equitable access What do we mean by One Health? It is an approach to designing and implementing programmes, policies, legislation and research in which multiple sectors work together to achieve better outcomes. This is critical for tackling the pandemic of drug-resistant infections, which moves silently between humans, animals and environments. Treatments will only be successful if antimicrobials are available to everyone, including in low- and middle-income countries, and used responsibly and appropriately. While the public and private sectors

have worked flexibly during COVID-19, there have been significant challenges to equitable access to medical countermeasures. This will delay the end of the pandemic. Such inequity should not be a feature of the response to drug-resistant infections. Furthermore, the reality and know-how of low- and middle-income countries must be a part of a comprehensive response. Global partnerships for a global crisis One way to proactively address drug-resistant infections, to assure sustainability, equitable access and stewardship, is through not-for-profit partnerships. Such partnerships, unconstrained by commercial profitability requirements, can invest in preparing and responding to drug-resistant infections according to public health needs. These partnerships are well positioned to work with public and private sectors to develop and provide new antibiotics for those that need them, wherever they live. They can also work with governments, companies and communities in all countries. Yet to succeed, this work must be significantly scaled up now.

The last chance to reinvigorate AMR innovation The needs of small and medium-sized enterprises (SMEs) must be considered when reshaping the regulatory framework intended to incentivise AMR innovation. SMEs are keen to contribute to a dialogue with policymakers.

s we painfully enter a post COVID era, Europe is organising itself to ensure that it is not caught unawares in the event of a new pandemic. In this fight, antimicrobial resistance (AMR) is well positioned to take over the role of public enemy number one. While the last decade has been largely one of global reporting and political awareness, the time for action is now. Moving towards a regulatory big bang for AMR This year, evidence of the European Commission’s (EC) action has been mounting. In 2021, the EC

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launched the HERA (European Health Emergency preparedness and Response Authority). At the moment, the focus of it is predominantly on preventing deterioration on the COVID front, but the hope is AMR will soon be in its scope. In addition, 2022 will hopefully see a new consortium launching, funded by the Horizon Europe programme. The consortium will set the basis of the “Innovation Partnership” which is a legal framework created by the EC. The aim of the proposed partnership is to combine the support of R&D against AMR and the procurement of the antimicrobials that would

come from this support. Last but not least, the major manoeuvres around the recasting of pharmaceutical legislation have been launched, with a public consultation underway until December this year. At the heart of this review is how to better address unmet medical needs, in particular AMR. Even if it remains to be defined how all these initiatives will fit together, these major manoeuvres are clearly heading in the right direction, at least in intention.

Dr Hanan H. Balkhy Assistant Director-General for Antimicrobial Resistance, World Health Organization

Anthony Coates Board Member, BEAM Alliance

No second chance to succeed BEAM Alliance and its members are looking forward to these promising developments with enthusiasm and with a little concern, if the outcome is not suited to SMEs, it will not work. Access conditions to any type of market incentive must be transparent, predictable and recognised early, this includes eligibility criteria and size of the reward. Only then will an SME be able to raise the necessary funds to develop its product. SMEs are in the best position to anticipate what investors expect, so their voice must be heard. As author and screenwriter Alan Bennett once said, ”Sometimes there is no next time, no time-outs, no second chances. Sometimes it’s now or never.” This time is now for the AMR innovation ecosystem.

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New strategies for clinical trials are needed to combat AMR The continued threat of antimicrobial drug resistance (AMR) spawns a wide spectrum of anti-infective strategies. Daniel F. Sahm PhD, D(ABMM), FAAM Vice President Global Microbiology Services and Chief Scientific Officer, IHMA

Darcie Carpenter, PhD Director, Global Business Development, IHMA WRITTEN BY Mark Nicholls

Find out more at ihma.com

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r Daniel Sahm, who has worked in drug development for 30 years and is Chief Scientific Officer at IHMA, states that small molecule drugs developed for infectious diseases are not maintaining the level of effectiveness needed to keep up with AMR. Finding new innovative approaches This continued threat of AMR among clinically relevant bacteria has resulted in the pursuit of newer strategies to develop products for the management and treatment of bacterial infections. These new strategies go beyond small molecules such as the typical antibiotics (e.g. penicillins, cephalosporins, fluoroquinolones, etc) and venture into areas such as anti-virulence products, vaccines, immunomodulators, bacteriophage therapy and microbiome manipulations. These innovative approaches are scientifically exciting and provide many new paths forward. Complexity of trial design However, they also introduce many new challenges with regards to complexity of clinical trial designs, product manufacturing and the development of analytical methods. For these reasons, lab service providers who support all phases of anti-infective development, such as the IHMA, must be scientifically flexible and adaptive. New assay methods must be fully developed and validated in order to provide the necessary analytics, they also must be performed in a manner and volume that are consistent with the needs of clinical trial designs and timelines. These evolving strategies also present challenges to the microbiology diagnostic industry as many of the new analytical methods may need to be adapted for routine testing in clinical microbiology laboratories throughout the world. Keeping ahead of AMR As the focus for these new therapeutic strategies evolves, clinical microbiologist Dr Darcie Carpenter says: “We must adapt these clinical trial testing approaches for routine laboratory use as we try to move these therapeutic agents through the approval processes.” So, the fight against bacterial diseases continues with an opponent that has the full genetic capability to fight back. “We probably cannot fully win the battle against AMR, but we certainly cannot afford to lose it,” says Dr Sahm. “At this point, we are simply trying to stay one step ahead of this public health challenge.”

Dr Alexis Rideau CEO, Deinove

Back to nature: dark biological matter can lead us to new antibiotics

Can nature and bacteria themselves provide us with the next-generation of antibiotics to fight superbugs? We strongly believe the answer is yes.

pproximately two out of three antibiotic classes used today find their origins in natural compounds derived from bacteria or fungi. Most of them are small molecules, called secondary metabolites, produced by bacteria themselves. Over 100 antibiotics have been developed since 1928 when the first antibiotic, a natural compound, penicillin, was discovered. But most of these antibiotics only belong to just over 20 different chemical families which were discovered between 1929 and 1962, stemming mostly from the Actinobacteria phylum. Since then, new antibiotics have resulted from synthetic modifications of pre-existing ones. Only three new classes (oxazolidinones, lipopetides and malacidins) have been brought to the market.

The global antibiotic pipeline is not just lacking in numbers: we need new, efficient chemical scaffold.

underlying metabolic potential and reveal new classes of antibiotics. The global antibiotic pipeline is not just lacking in numbers: we need new, efficient chemical scaffold. Fermentation route to produce molecules Nature is not just the source of new molecules; it is also one of the most efficient ways of production. Fermentation is often the best – and sometimes the only – route to produce complex molecules like antibiotics in a quantitative and cost-efficient manner. Small molecules produced by fermentation are often overlooked because they are not considered “innovative enough”. It is a big mistake: the science and industrial processes behind them are very complex and require cutting-edge technologies and expertise. Sometimes, traditional natural methods being updated to modern technologies are just what the doctor ordered. We need to pursue this route and that is what we dedicate our innovative discovery platform to at Deinove. Find out more at deinove.com

Advances in technology Meanwhile, recent evidence suggests an estimated one trillion microbial species populate planet Earth. Only 0.1% of them have been identified and even fewer have been cultured. This microbial “dark matter” has remained overlooked for decades due to their low abundance, their low detection rates and the difficulty in cultivating and isolating them. But times have changed: new technologies such as microfluidics, metagenomics and synthetic biology, give us the possibility to exploit the almost unlimited

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Thomas Cueni Director General, IFPMA

The imminent threat of AMR and why we must prepare

Tackling AMR through addressing sociocultural inequities

AMR is a silent pandemic that needs attention now. Globally, we need to take action or it will continue to claim lives.

t’s been 18 months since the world was struck by the COVID-19 pandemic. Though vaccines and treatments were developed in less than a year, politicians and experts will meet at a special World Health Assembly this November to discuss future pandemic preparedness. So, it is somewhat ironic that it is during the same month that we mark the silent pandemic of antimicrobial resistance (AMR). World Antimicrobial Awareness Week sounds the alarm on the devastating global impact of drug-resistant infections, which have the power to set back modern medicine by 100 years. We know that more than 700,000 people die each year due to AMR. By 2050, AMR could claim as many as 10 million lives annually and cost the global economy up to USD 100 trillion.1

For sustained improvement in antibiotic prescribing, we need to understand the factors that influence their usage.

The way forward We need new economic incentives for a robust antibiotic pipeline; valuation of antibiotics that acknowledges the value antibiotics deliver to society and reimbursement reforms to maintain availability, access and appropriate use of antibiotics on the market.4 Pandemic preparedness requires an innovation ecosystem where new treatments can thrive. Imagine if the world was ready.

Dr Peiffer-Smadja Fellow in Infectious Diseases, Hopital Bichat, Université de Paris, Imperial College London

References 1. O’Neill, J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. Review on Antimicrobial Resistance. 2014. Available at https://amr-review.org/sites/ default/files/AMR%20Review%20Paper%20 -%20 Tackling%20a%20crisis%20for%20 the%20health%20and%20wealth%20of%20 nations_1.pdf 2. https://www.gov.uk/government/ publications/100-days-mission-to-respond-tofuture-pandemic-threats 3. https://amractionfund.com/resource/ the-amr-action-fund-announces-its-firstnon-industry-investments-raising-anadditional-us140-million-toward-addressingantimicrobial-resistance-amr/ 4. https://www.ifpma.org/resource-centre/globalprinciples-on-incentivizing-antibiotic-rd/

Dr Esmita Charani Research Lead for Practice Design and Engineering at the NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Research Lead for Executive Committee of ESCMID ESGAP

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he relationship that we have developed with antibiotics is complex and driven by many factors beyond health and disease. We have long considered antibiotics to be miracle drugs due to their ability to treat diseases, however, their overuse is now costing human lives. Antimicrobial resistance (AMR) is now a major threat to healthcare and our global economy, with burden of disease and death highest where there are least resources. Antibiotic prescribing is a social process Infectious diseases are becoming an increasing threat in human populations. Their management is the responsibility of clinicians across different specialties. It is estimated that up to one-third of antibiotic prescriptions may be inappropriate, and this widespread, inappropriate use puts patients at risk of AMR and treatment failure. Drug resistant infections and AMR are driven by sociocultural factors that require a multidisciplinary response. In places where there is a lack of access to resources such as expertise in infectious diseases, laboratories and access to tests to diagnose infections, the likelihood of misusing antibiotics is much higher. For prescribers, the fear of risk of treatment failure in their patients often outweighs the risk of AMR. Additionally, entrenched hierarchies and social norms within healthcare mean that it remains difficult to challenge behaviours that result in inappropriate antibiotic use. New drugs won’t fix the problem, unless we optimise use of existing ones Much of the discourse on AMR remains around developing new agents but this can take a long time and require a lot of investment. Whilst it remains critical that we find new drugs, unless we understand how and why we continue to misuse existing antibiotics we will not make progress with managing the challenge of AMR.

Image provided by IFPMA

No market, no incentives In response to COVID-19, the G7 put forward a vision for a 100 Day Mission to respond to future pandemics, making available diagnostics, therapeutics and vaccines within 100 days of an emerging health threat.2 However, in the years that it has been on the G7 agenda, no bold vision has been proposed to develop new antibiotics that can be used as a last resort when all existing antibiotics have proven to be ineffective against bacteria. The previous decades in antibiotic innovation have been sparce,

as there is no market to incentivise research and development for new antibiotics. Last year, the industry stepped up and created the AMR Action Fund, the world’s largest publicprivate partnership supporting the development of new antibiotics.3 This will provide a valuable boost to innovation but, alone, it is not sufficient.

You can read more about the strategies to optimise antibiotic use at wellcome.org thelancet.com

To do this, we need to: 1. Develop strategies that are flexible to the needs of different context and populations. 2. Build capacity for research into understanding how innovations can be implemented in different resource settings. 3. Engage with patients and the public to raise awareness about the consequences of antibiotic use and misuse. 4. Work with policy makers to ensure equitable access to effective drugs for all.

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Power to the people in AMR labs worldwide

Infection monitoring in Nigeria Courtesy CDC / Visa Tyakaray

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The genomic sequencing revolution is enabling researchers in low and middle income countries to swiftly tackle challenges from AMR to COVID-19 as they emerge.

A Professor David Aanensen Director, NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, University of Oxford

MR threatens healthcare at every level in every country. Partnerships are essential to enhance strategic surveillance in key countries worldwide. Our partners are equipped with genome sequencing and analytic expertise to map the emergence and spread of priority pathogens and variants of concern. An example of this is the Ibadan University team, who confirmed an Acinetobacter hospital ICU colonisation outbreak and was able to support the Nigeria Centre for Disease Control. In the Philippines, we have helped control outbreaks in multiple hospitals. Agrosavia, our partner in Colombia, was able to detect and confirm a serious

outbreak of salmonella in Calí. Our partners are also helping influence national policy and authoring reports for the World Health Organization. Introducing global AMR surveillance Last year, our partnership adapted their sequencing capacity to tackle COVID-19. Our India partners are now a nationally accredited COVID-19 testing lab and Agrosavia is scaling up and training other labs across South America. Our ambition is to establish a globally distributed genomic surveillance network for AMR that generates actionable data which will enable policy makers and public health programmes to make informed decisions in real

Financing the fight:

the role of investors in the fight against AMR The global risk of antimicrobial resistance is increasing. Investors are harnessing their power to turn the tide on AMR.

T Jeremy Coller Chair, FAIRR

Find out more at bit.ly/3k7UA5Q

he COVID pandemic has seen antimicrobial resistance (AMR) become a key item on the G7’s agenda, with health and finance ministers committed to ‘curb the silent pandemic’. Failure to tackle AMR could take USD 100 trillion of value out of the economy, worse than the damage of the 2008 financial crisis. Antibiotics in agriculture Investors increasingly recognise the animal agriculture sector is particularly exposed to risks as it is the leading user of everyday antibiotics. An estimated 70% of global antibiotic use occurs in animal farming, antimicrobials are used to enhance growth and for routine prophylactic use due to the crowding of animals in tight spaces.1 Investors working through the FAIRR Initiative (Farm Animal Investment Risk & Return) successfully engaged with 20 of the largest restaurant chains to urge them to adopt policies to

reduce antibiotics in their food supply chains. Animal pharma is a risky business Investors have turned their attention to the USD 47.1 billion animal health sector which provides therapeutic products and veterinary medicine for animals, urging the sector to limit exposure to AMR. FAIRR’s report, Feeding resistanceAntimicrobial stewardship in the animal health industry, finds none of the largest 10 publicly listed animal health companies have a comprehensive strategy to reduce the impact of AMR.

time. This will mean we can catch up with the evolving pathogens and eventually we hope to outsmart them. To achieve this, we are working alongside other NIHR funded groups. For example, the NIHR Global Health Research Unit on Tackling Infections to Benefit Africa (TIBA) partnership has enabled the development of viral sequencing capacity in 13 countries across Africa, informing national and regional responses to COVID-19 working closely with the WHO Africa Regional office. In Asia, NIHR partners with WHO TDR to coordinate operational research in AMR control in healthcare facilities across Nepal and is working in other low-income settings worldwide. This work has generated many important research papers and is informing government policy, WHO guidelines and helping clinicians and researchers tackling disease threats all over the world. It is a privilege to be able to support this global effort. NIHR supports high-quality global health research for the direct and primary benefit of people in low and middle income countries. NIHR funded programmes and partnerships are developing and strengthening health R&D capacity, capability and expertise in more than 50 LMICs. For more information visit: nihr.ac.uk

investments must mitigate, not exacerbate, the impact of AMR. As part of this initiative investors are actively engaging with portfolio companies. Examples include BMO Global Asset Management and Nordea Asset Management who are engaging with companies on AMR risk topics including R&D, waste management and stewardship. Like freshwater or forests, antibiotics are a global resource we need to preserve and use appropriately. The finance sector needs to encourage responsible use to protect the long-term efficacy in humans and animals. Current food supply chains are not sustainable, nor is the trajectory of AMR usage in intensive agriculture.

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www.fairr.org

References 1. Van Boeckel, Thomas P., et al. “Global trends in antimicrobial use in food animals.” Proceedings of the National Academy of Sciences 112.18 (2015): 5649-5654.

Adopting an AMR lens We have recently launched the ‘Investor Action on AMR’, a coalition between FAIRR, Access to Medicine Foundation, Principles for Responsible Investment (PRI), the UK Government Department of Health and Social Care and 16 global institutional investors. Investors committed to adopt an ‘AMR lens’ when making investment decisions. This means

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It is essential to focus on preventing infections to tackle AMR We are living through a global pandemic, with 5 million deaths associated with COVD-19 since the start of 2020. However, the threat of antimicrobial resistance (AMR) continues to loom.

he Global AMR Review Study highlighted that 700,000 people die of antimicrobial resistant infections each year and that without urgent action, the death toll could rise to as many as 10 million deaths annually by 2050, causing a 3.8% reduction in annual gross domestic product (GDP).

Dr Diane Ashiru-Oredope Lead Pharmacist, HCAI, Fungal, AMR, AMU & Sepsis Division, UK Health Security Agency

Top 10 global threats to humanity We have seen how this pandemic is affecting the most vulnerable in our society, causing devastation to the most disadvantaged people. AMR is no different, making those living in low- and middle-income countries and the marginalised communities in high income countries disproportionately vulnerable. The World Health Organization declared AMR one of the 10 global health threats facing humanity in 2020. COVID-19 is also exacerbating AMR. While co-infection of COVID-19 and bacterial infection remains low - 6·9% of those diagnosed with COVID-19, antibiotic prescribing occurred in more than 70% of patients diagnosed with COVID-19 infection. These actions can worsen the state of AMR as a result of overuse of antibiotics due to the pandemic. Antimicrobial consumption and resistance during the pandemic The data from the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) shows

Working together to stop a ‘silent pandemic’

that antibiotic consumption in the community reduced during the initial stages of the pandemic. This highly correlated with reductions in other seasonal respiratory infections due to reductions in social mixing and changes in health seeking behaviour, access and delivery. However, the use of antibiotics, especially antibiotics of last resort, increased in hospitals as well as the proportion of bloodstream infections detected with resistance to one or more antibiotics. Continuing education of good practise Although competing priorities to deal with the pandemic have led to reduced focus on strategies to tackle antimicrobial resistance specifically, the enhanced focus on infection prevention and control to prevent COVID-19 will prevent other infections avoiding the need for antibiotics. We need to continue to educate and inform the public and healthcare workers on how infections develop through the chain of infection and breaking it through practices such as good handwashing, catching coughs and sneezes (including the use of face coverings) and regular cleaning at home, in the office and in healthcare settings. It is important that the public and healthcare professionals continue to focus on reducing the incidence of infections and subsequent development of antibiotic resistant infections.

Technician Sandy Cheng helps Dr. Sophie St. Hilaire on a nanobubbles research project in Hong Kong.

The UK’s global partnerships are fighting against drug resistance.

B C/ DR

©I

A Professor Dame Sally Davies UK Special Envoy on Antimicrobial Resistance

ntimicrobial resistance (AMR) is happening right now across the world. The United Nations and its member countries are committed to ensuring healthy lives for all by 2030. The Sustainable Development Goals depend on us ensuring everyone, everywhere is safe from this threat which does not respect borders. International collaboration This year marks a turning point for AMR global policy making. Under the UK’s G7 Presidency, G7 Leaders announced bold steps on AMR and agreed that they need to act right now. G7 Health Ministers have committed to improve antimicrobial innovation, supply chain resilience and knowledge

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y ta

about AMR in the environment. These developments could ensure that people around the world have access to the right treatments at the right time – and that they won’t cost the earth. Data enables evidence-based decisions When high-quality AMR data is produced and shared locally, nationally and globally, then decision-makers can act appropriately. The UK Government’s Fleming Fund is a UK Aid programme supporting countries across Africa and Asia to collect and use AMR data effectively. New data, partially funded by the Fleming Fund and published soon in the Lancet, will show the true burden of AMR around the world.

Dr Susan Hopkins Chief Medical Advisor, UK Health Security Agency

Never has the Fleming Fund’s work, helping countries to collect high quality data to inform good AMR policy, been more important. The Fleming Fund’s country partnerships strengthen health systems, ensuring labs have access to clean running water, installing cutting-edge equipment and training laboratory staff. A clean, green way to cut antimicrobial use in fish farming The Global AMR Innovation Fund is a UK aid fund that works with international researchers to develop new interventions and reduce antimicrobial use. Nanobubbles’ peculiar physical and chemical properties are already being exploited to clean wastewater. Now researchers are hoping to repurpose this technology to combat antimicrobial resistance in food production. Nanobubbles could kill pathogens, without harming the fish and shrimp. We all play a role in tackling AMR Everyone can work together to address AMR. From washing your hands to handling antibiotics with care, we can protect our antimicrobials and our world. With every single one of our international partners and friends, the UK hopes to strengthen global health security for all, for good.

The full article can be found online at globalcause. co.uk

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When doctors have minutes, why must tests take days?

AMR is an insidious pandemic threatening modern medicine. It will not be subdued or overcome by one single approach.

Existing diagnostic tests to determine infection by specific bacteria and the best treatment in primary care can take up to 2-3 days to produce a result – a process that hasn’t changed much throughout the age of antibiotics.

or a GP who usually has to prescribe antibiotics before any test result is available, the wait is too long. The same can be said for a patient who needs to know whether antibiotics will help them recover any faster or not, or if they have a lifethreatening bloodstream infection or sepsis that needs immediate antibiotic treatment.

We need new antibiotics and improved preventative measures, but we also need faster and more accurate tools to disrupt the days of delay that can currently make antibiotic stewardship a difficult guessing game.

Preventing the rise of AMR In 2014, the £8 million the Longitude Prize was established. We asked the British public to Faster, more accurate tools needed choose between six existential Antimicrobial resistance (AMR) is challenges that the prize could an insidious pandemic threatening focus on. Following a national modern medicine. It will not be vote in partnership with the BBC, subdued or overcome by one single the overwhelming choice was ai16371617657_T2_1186 Ad_4.pdf 1 11/17/2021 10:09:31 AM approach; itNew is aScientist battle AMR on multiple ‘antibiotics’ - how can we prevent fronts requiring many solutions. the rise of resistance to antibiotics?

The Longitude Prize has called on innovators to develop accurate and affordable diagnostic tests at point-of-care that will improve antibiotic use and could impact on AMR. £8 million will be awarded to the first team to meet the prize’s seven mandatory criteria whose test can identify if antibiotics are necessary, and if so, which to prescribe. £8 million is there to be won. However, the real prize will be a new generation of point-of-care diagnostic tests, providing accurate results for bacterial infections, not in days, but minutes.

Chris Butler Professor of Primary Care at the University of Oxford and Chair, Longitude Prize Advisory Panel

Globally, 55 teams are developing novel point-of-care tests in pursuit of the prize. Although any one of the currently registered teams may win, new teams are still welcome to register to compete at longitudeprize.org Next year the prize will come to an end – the final deadline to apply is September 2022.

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Facilitating scientific collaboration to accelerate antibiotic discovery An antibiotic data-sharing platform is helping scientists around the globe tackle the ongoing threat of AMR.

ntibiotic resistance is a dire and growing public health threat, with the United Nations projecting that by 2050 drugresistant diseases could cause 10 million deaths globally each year. New antibiotics are urgently needed to protect patients from antibiotic-resistant “superbugs,” but low returns on investment have led many pharmaceutical companies to leave the field of antibiotic research and development. Collaborating through open platforms To preserve a treasure trove of scientific knowledge that might otherwise be lost, in 2018 The Pew Charitable Trusts created the Shared Platform for Antibiotic Research and Knowledge (SPARK), a tool designed to gather data from discontinued research and other sources and made it available to scientists carrying on the work around the globe. Scientists can collaborate on the open platform; learn from past successes and failures; and build on the knowledge base created by fellow researchers. In the past three years, more than 800 users in over 60 countries have engaged with SPARK.

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research groups

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11,223

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compounds received

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CO-ADD screening activities have helped research groups across the world. To date, collaborators have benefited from free screening of their compounds.

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Without new antibiotics, the world risks a return to the days when a simple schoolyard scrape could lead to a deadly infection.

Paid for by The Pew Charitable Trusts

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The platform functions as a virtual, cloud-based laboratory, enabling scientists to contribute data and insights as well as generate new ideas for future drugs and currently focuses on the most dangerous superbugs: resistant Gram-negative bacteria. SPARK hosts information on nearly 160,000 compounds and more than 120,000 associated data points from scientific journals and data contributed by individual users and companies including Merck, Kyorin, Novartis, and Achaogen. Discovering new antimicrobial drugs Pew is now transferring SPARK to The University of Queensland’s Community for Open Antimicrobial Drug Discovery (CO-ADD). Founded in 2015 as a not-for-profit initiative

based at UQ’s Institute for Molecular Bioscience, CO-ADD’s goal is to help discover antimicrobial drugs by offering free screening of diverse synthetic chemical compounds submitted by academic collaborators. CO-ADD has tested more than 300,000 compounds and identified more than 2,500 that are antimicrobial at concentrations that are nontoxic to human cells, which could be starting points for future antimicrobial drugs. CO-ADD has been a significant contributor of SPARK data and CO-ADD’s chemoinformatics expert, Dr Johannes Zuegg, helped advise Pew on SPARK’s development. Both Pew and CO-ADD aim to foster collaborations to drive antibiotic innovation as the threat of untreatable superbugs grows. Without new antibiotics, the world risks a return to the days when a simple schoolyard scrape could lead to a deadly infection. Moreover, without effective antibiotics, medical procedures we take for granted today—chemotherapy, joint replacements and liver transplants, to name a few—would be too dangerous to undertake. Yet even though antibiotics are indispensable to the conduct of modern medicine, the global development pipeline for new antibiotics is running dry.

David Hyun M.D. Director, The Pew Charitable Trusts’ Antibiotic Resistance Project

Mark Blaskovich Associate Professor, The University of Queensland; Director, Centre for Superbug Solutions at the Institute for Molecular Bioscience and co-founder of the Community for Open Antimicrobial Drug Discovery at The University of Queensland

Public benefit to the global community Government agencies, non-profit organisations and research institutions are recognising the need to fill the gap. The comprehensive, open-access knowledge base is a public benefit to help the global community come together to discover effective, new antibiotics. CO-ADD’s goal is to use its expertise in identifying antimicrobial compounds to build on SPARK’s success and give the platform a secure, long-term future. CO-ADD will integrate SPARK with its own open access initiatives, recruiting more data and expanding the content to include Grampositive compounds, cytotoxicity test results and bacterial isolate profiles from both academic and industry scientists. Working closely with research journals and organisations leading the way on antibiotic resistance—including its current collaborators, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and the Global Antibiotic Research and Development Partnership (GARDP)—CO-ADD will optimise the usability of the SPARK database, and further anticipates launching a predictive modelling component so that SPARK users can test artificial intelligence or machine learning tools.

Pew is proud that its work on SPARK will be carried on and broadened at The University of Queensland through CO-ADD. To learn more, visit spark.co-add.org or email spark@co-add.org Current SPARK data can be accessed through Collaborative Drug Discovery’s Vault at collaborativedrug.com/spark-data-downloads

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