Antibiotic resistance Campaign 2016

NOVEMBER 2016

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Antibiotic resistance GLOBALHEALTHACTION.CO.UK

Lord Jim O’Neill The top government advisor explains why less is more in antibiotic prescribing TRACEY GUISE, BSAC

The importance of global education for healthcare communities P3 GLOBAL EFFORT

Professor Mark Wilcox breathes fresh air into the anti-pneumonia campaign P8

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Dame Sally Davies The chief medical officer on leading the war on drugs-resistant superbugs P4

Barbara Fallowfield Why accurate diagnostics have a vital role to play in tackling drug resistance P6

Professor Ramanan Laxminarayan Tackling AMR will require the translation of a global vision for change into localised action

Saving antibiotics through the One Health agenda Antibiotics are medicine’s wonder drugs and the mainstay of modern healthcare. In their presence we can save lives, extend life expectancies, improve the quality of life and support commonplace and progressive health therapies such as chemotherapy for cancer, heart transplants and joint replacement therapies

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heir success is also their downfall as increased use has led to an increase in antibiotic resistance (AMR) that threatens the effectiveness of antibiotics AMR is an unavoidable and inevitable consequence of antibiotic use that has been accelerated by the global use, overuse and misuse of antibiotics over the decades.

According to the recently published AMR review, it will be directly responsible for 10 million deaths Follow us

annually by 2050 as the emergence of multi-drug resistant infections, for which there are few or no effective antibiotic cures, increases.

The magnitude of the crisis has not gone unnoticed. On 29 September 2016 the United Nations (UN) issued a declaration calling for action only the fourth time in its 70 year history that a health issue has been addressed. AMR now sits alongside HIV and Ebola for the gravity of the threat it poses to humankind.

The declaration offers an

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Professor Dilip Nathwani OBE President, British Society Antimicrobial Chemotherapy, honorary professor of infection, Ninewells Hospital, Dundee

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unparalleled opportunity for change. The solution is multi-faceted but at its heart lays education about the causes and actions to ensure antibiotics are used responsibly, effectively and only when absolutely needed. Far more challenging is how we deliver and implement the solutions globally, taking account of cultural, geographical, structural and economic differences.

This campaign offers an opportunity to demonstrate to all the value of adopting a “One Health @MediaplanetUK

Approach” to AMR, defined as the collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals and our environment and recognising that the health of people is connected to the health of animals and the environment.

Through concerted efforts across all sectors, we can bring about the changes needed to stem AMR and preserve effective antibiotics for use now and in the future.

Please recycle

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Global education for healthcare communities

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By Tracey Guise

Education of healthcare professionals about how to be effective and efficient prescribers of antibiotics is essential if we are to reduce antibiotic resistance rates and minimise the impact of multi-drug resistant infections.

The challenge is how to deliver education across the globe that takes account of the differences faced across the continents – as cultures, economics and healthcare structures vary widely.

Tracey Guise Chief executive officer, British Society for Antimicrobial Chemotherapy

Within challenge there is opportunity. Whilst the differences of culture, finance and organisation of healthcare cannot be denied, neither can the fact that the principles of effective antibiotic prescribing should be the same the world over. Delivering core messages and education about effective prescribing globally are greatly assisted by the mobile data age in which we live, and a recent innovative global education programme is taking full advantage of this.

The Massive Open Online Course on Antimicrobial Stewardship – or MOOC-AS to those in the field – has provided access to free education on prescribing to all health economies internationally. Over 35,000 learners globally, including healthcare professionals and members of the public have registered for the course since its launch in September 2015. The course was developed by the British Society for Antimicrobial Chemotherapy (BSAC) in partnership with the University of Dundee.

The British High Commission Science and Innovation Office are working similarly, but within smaller global-community focussed projects.

Through its grant giving framework the commission is linking organisations such as BSAC with healthcare leaders in India, Russia and Africa to develop educational frameworks for the delivery of education on how to prescribe effectively. It is a lean and efficient way to share expertise and facilitate a reduction in antibiotic resistance through sustainable education programmes.

To succeed in tackling antibiotic resistance through education we must meet the diverse needs of all learners.

The examples described here are the early beginnings of what could be a revolution in the delivery of healthcare education through the creation of online global communities of learners who can share their expertise and borrow from others knowledge and experience.

Laura Piddock Professor of microbiology and deputy director of the Institute of Microbiology & Infection, University of Birmingham

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AntibioticDB

he current state of antibiotic discovery and development is insufficient to respond to the need for new treatments for drug-resistant bacterial infections. The process of antibacterial discovery, research and development has changed over the last decade with most of the new agents in clinical trials or recently approved, having been discovered in academia or small to medium sized companies. These have then been licensed or sold to large companies for development with the end goal of producing new drugs to use in patients.

However, early drug discovery and development, including the possibility of developing previously discontinued agents would benefit from a database of antibacterial compounds.

AntibioticDB, antibioticdb.com, is the first free, open-access database of antibacterial compounds. It includes over 1000 compounds, which are in one of the following categories: (1) discovery or hit to lead optimisation; (2) clinical trial; (3) awaiting approval, or recently approved for use in patients; (4) the compound has been discontinued. The database is simple to use: queries such as drug name or class are typed into a familiar search bar and then clicking on ‘search’.

This database will help people to know the reasons for not developing some compounds and the current status of development of compounds as they travel through the development pipeline.

Read more on globalhealthaction.co.uk and antibioticdb.com

With thanks to the British Society for Antimicrobial Chemotherapy for collaborating on the development of this campaign +44 121 236 1988 www.bsac.org.uk www.antibiotic-action.com www.antibioticguardian.com

0845 618 8224 enquiries@bivda.co.uk www.bivda.co.uk

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Dr Diane Ashiru-Oredope Pharmacist lead, AMR Programme, Public Health England

Partners in prescribing Forging partnerships with patients is the only way for the UK to successfully protect its antibiotic reserves.

When winter bugs strike, people can think that an antibiotic from the GP is the right treatment. But, according to Dr Diane Ashiru-Oredope, pharmacist lead for antimicrobial resistance at Public Health England, for most people there are far better ways to deal with these common ailments.

“A pharmacy can be a helpful port of call when you have symptoms of winter bugs ,” she says. “Pharmacists are experts in medicines, and they are easily accessible which can be helpful when it is not necessary or possible to see your GP immediately.

They can advise whether your symptoms need to be treated by a GP, and if not, they can help you choose the best over the counter remedies to manage your symptoms.”

Antimicrobial resistance (AMR) is now considered a global emergency and without effective antibiotics routine illnesses and basic operations will become more difficult to treat and more risky. NHS staff have all signed up to cut unnecessary antibiotic prescribing, and as the winter bugs strike, they are calling on the public to play their part to support prescribers in the responsible use of antibiotics. “It needs partnership to make sure that we make the best use of antibiotics and help save these vital medicines from becoming obsolete. There is also a need for preventive measures such as regular hand-washing, getting your vaccinations to control spread of infection as well as improved practice and education around antibiotics to promote their appropriate use, which will help slow down the development of antibiotic resistance. The Antibiotic Guardian website provides additional information on antibiotic resistance and simple actions all can take to help tackle antibiotic resistance,” says Ashiru-Oredope.

Leading the war on drugs-resistant superbugs Can you imagine a world where hip operations or caesareans were considered so risky some people may die? This could become a reality if we do not act

By Dame Sally Davies

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ntimicrobial resistance poses the biggest threat to global health. If not tackled, estimates suggest that by 2050, drug resistant infections could kill 10 million people a year across the world.

A year on from the first ever World Antibiotics Awareness Week, great progress has been made but urgent work is needed if we are to save modern medicine.

In the pre-antibiotic era, around 40 per cent of deaths were due to infections, now it is just 7 per cent. But this work could be reversed; and already drug resistant infections like TB, HIV and malaria kill more than 700,000 people annually according to estimates.

In a post-antibiotic era common infections and minor injuries could kill through infections.

Chemotherapy would risk untreatable infections and simple surgeries, such as hip operations, could become life threatening through drug resistant infections.

How we respond to this will not only define the next era of medicine but next chapter of human history. It truly is that important.

It is a complex issue and a global problem that will not be solved overnight. But everyone can help.

We must prevent infections through good hand washing and routine vaccination, including flu—

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PHOTO: BSAC KIND COURTESY OF C JAMIESON

Data collection is of the utmost importance in order to get a clear picture of global antibiotic use

which is known to increase the risk of acquiring a bacterial infection.

We must reduce the inappropriate use of antibiotics—they will not work on viruses. I urge people to trust their doctor or pharmacist when they say antibiotics will not help.

Every nation needs to take responsibility with a ‘One Health’ approach. We must work locally, nationally and internationally to get the best health outcomes for people, animals and the environment. The UK will continue our work helping lead the global effort.

Currently, we simply do not know the scale of the challenge we face.

Many parts of the world simply do not

Dame Sally Davies Chief medical officer

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collect data and this is clouding the global picture.

The good news is we are making great strides. Last year’s inaugural World Antibiotic Awareness Week was a big step in educating the world and through our UK Fleming Fund, we are investing £265 million in global surveillance capacity.

In September—after three years’ work—we secured a United Nations Declaration on antimicrobial resistance and 193 countries agreed to tackle drug resistant infections as a priority.

Now action will be taken to improve surveillance and regulations, help develop new antibiotics and rapid diagnostics and work to improve education.

Our international achievements are also being matched on the home front.

I am pleased to say total antibiotic consumption declined significantly between 2014 and 2015—by 4.3 per cent.

Antibiotic prescribing has declined across all healthcare settings for the first time thanks to the work of NHS staff.

But work must continue, we must lower antibiotic use in both humans and animals at home and worldwide.

Encouraging pharmaceutical companies to develop new antibiotics is another global problem that needs a global solution.

The world must come together to continue this fight and the coming years are absolutely crucial.

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Jorgen Skov Jensen Consultant physician, microbiology and infection control, Statens Serum Institut, Denmark

New diagnostics change the way sexually transmitted infections are treated

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iagnostic advancements have provided invaluable insight to help tackle the growing problem of antimicrobial resistance in sexually transmitted infections (STIs).

Whilst penicillin continues to offer an effective treatment for syphilis and azithromycin for chlamydia, finding an effective drug to treat gonorrhea and the less-known, but highly prevalent STI, Mycoplasma genitalium, poses a huge challenge.

Both infections have developed some resistance to all the antibiotics currently used to treat them, which is where diagnostics provide invaluable insight. The latest testing kits not only diagnose the condition: they can also detect specific drug resistance so the most effective antibiotic can be prescribed.

“The tests help us determine what drug the bacteria will be responsive to and in 40-60 per cent of patients we can effectively use a conventional cheap drug,” explains Jorgen Skov Jensen, consultant physician in microbiology and infection control at Statens Serum Institut, Denmark.

The downside is that the tests are not currently available at the point of care, so patients have to return for their diagnosis and prescription. “There is a tradition that says unless you treat someone right then and there you risk losing contagious patients. But the experience in Scandinavia show that’s not the case,” explains Jensen, who believes there needs to be shift in mentality from simply treating symptoms to managing the underlying conditions.

“In light of increased antimicrobial resistance, we need to move away from syndromic management to a situation where we diagnose the etiology of the condition before treating it with the correct antibiotics,” he explains. “Diagnostics can help us do that.”

Diagnostics are vital in tackling drug resistance A multifaceted approach is needed to tackle antimicrobial resistance, and accurate diagnostics have a vital role to play in containing the problem and finding a solution

By Kate Sharma

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t’s common knowledge that the misuse of antibiotics has exacerbated the problem of antimicrobial resistance (AMR). A failure to correctly diagnose many conditions correctly has led to drugs being used in far greater quantities than necessary.

“There has been a lot of emphasis on the push for ‘cheap diagnostics’ in recent years, which has completely reduced the value that diagnostics have to play in solving the problem,” explains Barbara Fallowfield, Managing Director of the British In Vitro Diagnostics Association (BIVDA).

“What’s equally concerning is that we have a tendency to focus on developing new diagnostics and ignore some of the tools already available.”

One of the tools already in use is the C-reactive protein test (CRP), which can be used at the point of care to detect if a patient has a viral or bacterial infection and if antibiotics should be prescribed. The test is already used in many European countries, including the Netherlands, Sweden and Germany, where fewer antibiotics have been prescribed as a direct result.

Despite the fact that the CRP has been around for more than a

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Rapid diagnostics can be used at the point of care, such as in a GP surgery, to help diagnose an infection

PHOTO: THINKSTOCK

decade and more than 19 pilot studies carried out, it’s still not widely used in the UK, something Fallowfield feels needs to be addressed.

“It all comes down to changing behaviour,” she explains. “There are questions about who will pay for it and who will conduct the tests. Rather than being seen as an expense, diagnostics need to be seen as part of the solution with a greater willingness to adopt the test and implement it effectively.”

One of the recommendations made

by Jim O’Neill in the much anticipated Review on AMR, published in May this year, was that by 2020 mandatory testing should take place in all

Barbara Fallowfield Managing director, British In Vitro Diagnostics Association (BIVDA)

high-income countries before antibiotics are prescribed. In order to achieve this, more funding is needed and authorities need to do more to incentivise the use of rapid point-of-care diagnostics.

The report also calls for a more multinational approach to innovation in diagnostics. One initiative aimed at kick-starting research is the Longitude Prize, which will award £10million to a project that provides a cost-effective and easy-to-use test for bacterial infections that will allow health professionals worldwide to administer the right antibiotics at the right time.

“It’s really exciting to see such investment in research and

development in this area,” says Fallowfield. “But it needs to go handin-hand with greater use of the tools we currently have, innovation of existing resources and better surveillance so we have a global picture and can target support appropriately.”

When taking on the ‘biggest global health threat,’ there is no easy solution, which is why investment in all aspects of research and development, including diagnostics, is vital.

Read more on globalhealthaction.co.uk

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Dr James D Chalmers Senior clinical lecturer and honorary consultant physician, University of Dundee

Signs and symptoms of pneumonia

Patients with pneumonia nearly always have one of the main chest symptoms, particularly cough, shortness of breath and chest pain. The cough may be productive of sputum. The chest pain is often described as sharp and gets worse when patients breathe deeply, as the inflamed linings of the lung rub together.

Other important symptoms include fever, stopping eating, extreme tiredness, sore muscles/joints and sometimes diarrhoea and vomiting. It is important to remember that pneumonia often affects the elderly who may be less able to report their symptoms. Sometimes the only sign of pneumonia in patients with dementia, for example, is a loss of mobility and a worsening of mental state or agitation.

It is common misconception that pneumonia is always severe and always requires admission to hospital. It is estimated that 80 per cent of pneumonia cases are treated in the community

by GPs and so sometimes the above symptoms can be ignored or misdiagnosed as being due to a virus.

Breathing fresh air into the antipneumonia campaign Global efforts to fight communityacquired pneumonia are welcome, says Professor Mark Wilcox, Consultant Microbiologist, Leeds Teaching Hospitals (LTHT), and Professor of Medical Microbiology at the University of Leeds

By Ailsa Colquhoun

What to tell your GP Pneumonia is often diagnosed using a chest x-ray, but not every cough needs an x-ray as most are self-limiting and due to viruses.

Key information to give your GP will help them decide if you need an antibiotic and/or an x-ray • How long have you had the symptoms?

• Do you have pain in your chest when you breathe?

■ This is unusual with viral infections and makes pneumonia more likely.

• Do you have any other serious conditions?

■ Pneumonia can be more severe in patients with heart disease, COPD and diabetes among others.

• Have you travelled abroad recently?

■ Some infections are more common elsewhere in the world.

• Have you taken any antibiotics recently?

• Are you able to eat, drink, take medications and mange at home?

■ Most pneumonia can be treated at home, but if nausea and vomiting mean you can’t keep tablets down, or symptoms are severe then admission to hospital may be needed.

What causes communityacquired pneumonia (CAP)?

How much of a concern is CAP?

The bacterium Streptococcus pneumoniae is very common and at some point in our lives most of us will carry it harmlessly. But, in some cases, particularly virulent types of the bacterium invade the lungs and cause community acquired pneumonia (CAP); this can also occur following flu or other illness. S. pneumoniae can also enter the blood stream, where it can cause potentially-fatal problems such as sepsis, or other serious infections such as meningitis.

According to the World Health Organisation, pneumonia accounts for 15 per cent of deaths of children under five years old; in 2015 920,000 children died around the world because of pneumonia. But, it’s not just a problem in the developing world, and nor are only children affected. In the UK, pneumonia affects around eight in 1,000 adults each year, with infection rates highest in the autumn and winter. People who are elderly or who have compromised immune systems are most at risk.

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Global Macrolide Resistance Rates in Select Regions

Europe Austria 10.5% USA 48.4%

Belgium 24.8% Denmark 4.2% Asia Pacific China 96.4%

France 30.0% Germany 9.2% Latin America 36.1%

Hong Kong 75.5%

Italy 29.0%

Japan 61.1%

Spain 26.7%

South Korea Thailand 44.3% 77.7%

UK 4.7%

Malaysia 32.7%

My research involves analysing funding trends for infectious disease research. The UK is a big contributor to global health research, but our analyses show that the amounts of money spent on pneumonia have been quite low, relative to the worldwide number of deaths. There is, for example, greater ‘investment per global death’ for influenza and tuberculosis, and we concluded that research for pneumonia should increase accordingly. Encouragingly there have been increases in the numbers of funded pneumonia-

Are effective treatments available?

S. pneumoniae is still treatable with most commonly available antibiotics, but the concern is that the bacterium is becoming more resistant to some front-line agents. We see this resistance in countries including the US, Italy and Greece, as well as in Asia. The pharmaceutical industry is aware of this problem and new drugs are in development, although solutions are not quick or cheap to develop.

Why should ‘foreign’ microbes concern Britain?

Professor Mark Wilcox Consultant microbiologist, Leeds Teaching Hospitals (LTHT), and Professor of medical microbiology, University of Leeds

Taiwan 84.9%

Asia Pacific 72.7%

related studies in recent years and hopefully that upward trend will continue. Interventions around the world, such as recent progress in rolling out the ‘pneumococcal’ vaccine is also very helpful but there is still a lot to learn, and a well-funded research program can help provide that knowledge and greatly reduce both deaths and numbers of new cases of this devastating disease.

Dr Michael Head Senior research fellow at the University of Southampton

If you just think about the number of Brits who travel to Disneyland or Thailand each year, you must ask the question: “What are they bringing back besides souvenirs?” As part of every patient’s clinical ‘work up’ the physician should ask about recent travel and other illnesses, and use this information to understand the potential for antibiotic resistance when choosing the most appropriate therapy.

What can be done to reduce CAP infections?

Globally, measures are in place to protect, prevent, and treat pneumonia in

children. In the UK, eligible adults can have free NHS flu or pneumonia vaccines and, for the others, these are also available privately from pharmacies and GPs. Staying well this winter, for example, through good hygiene will also help, as will taking care of ourselves if bugs do strike. Globally, there is a renewed effort to ensure that effective antibiotics for CAP are available. CAP is a serious problem that the world, on a global level, is now trying to address.

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Creating Differentiated Antibiotics For more information go to: www.CABPCounts.com

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Why less is more in antibiotic prescribing

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Dr David Pardoe Head of growth projects, MRC Technology

Rethinking drug research, before it’s too late

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s we face the prospect of living in a ‘post-antibiotic’ era, there is renewed urgency to rethink the way we approach both the research and the funding of drug innovation.

“In developing new drugs we typically build on the research we’ve done in the past,” explains Dr David Pardoe, Head of Growth Projects at MRC Technology. “But we need a new approach.”

With the rapid increase in multi-drug-resistant (MDR) gram-negative bacteria, our tools are no longer fit for purpose. Fewer than half of the 39 antibiotics currently in development are effective against these bacteria. So scientists need to go back to the basics and understand the characteristics of the bacteria before developing new drugs.

“This stage of innovation is typically expensive and hard to get funding for,” explains Pardoe, which is why MRC Technology is advocating an alternative approach that focuses on bringing together organisations already working in this field to pool their resources and knowledge. Unlike other fund-based models, this collaborative approach sees organisations working together to define the problem and create insights that can be used much more widely.

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Reducing demand for antibiotics through better diagnostic support is the only way to avoid an antibiotic ‘apocalypse’, says top Government advisor Lord O’Neill

By Ailsa Colquhoun

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overnment advisor Lord O’Neill has urged global leaders to take a demand reduction approach to tackling the challenge of antimicrobial resistance (AMR). Calling on policy-makers to think more widely than bringing new drugs to market, he said: “Experience shows us that new drugs will eventually become victim of drug resistance. The only way is to reduce demand for antibiotics in the first place.”

In Lord O’Neill’s view, one of the most effective ways to facilitate demand reduction is to expand the use of diagnostic testing. Some self-testing equipment bought over the counter or point of care tests used by healthcare professionals in the com-

munity are already marketed in the UK to help front line patients and practitioners to distinguish between a range of viral and bacterial infections, and to identify specific microbes and their antibiotic resistance characteristics. Experts consider this a win-win policy: patients gain from more rapid use of effective antibiotics and society gains from less indiscriminate use of antibiotics, a major factor driving the emergence and spread of AMR. But better tests are needed and those that exist already are often under-used, as it can be cheaper to pay for an antibiotic ‘just in case’ than to pay for a diagnostic test.

Improved use of diagnostics is just one aspect of campaign to tackle AMR. In a review published earlier this year, Lord O’Neill

At the forefront of antimicrobial chemotherapy An inter-professional organisation with over 40 years of experience and achievement in antibiotic education, research and leadership. Dedicated to saving lives through appropriate use and development of antibiotics now and in the future.

www.bsac.org.uk www.antibiotic-action.com Charity no: 1093118

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PHOTO: AMR REVIEW

makes 10 recommendations to tackle AMR – a phenomenon likely to bring on an ‘apocalypse’, according to England’s chief medical officer Dame Sally Davies.

By reducing doctors’ prescribing, curbing use of the drugs in farm animals and incentivising drug companies to invent new antibiotics, the world will avoid a return to the days when conditions such as ‘the old man’s friend’ – pneumonia – and even childbirth, could end in death from infection. Encouraging Big Pharma to do its bit in drug development will be ‘pay or play’ policies that reward innovation and penalise nonparticipants, Lord O’ Neill says.

Endorsed by two prime ministers – and more recently, the G20 nations and

fourth health topic to be addressed by the Assembly in its 71-year history.

With the baton now passed to Germany, which takes on the presidency and will host the G20 summit in 2017, the hope is that the commitments made this year by global leaders will soon be realised. Lord O’Neill says: “The response to my report has certainly been encouraging. We have achieved a decisive environment in which to pursue action. But we must see the stage we are at now as only the end of the beginning. As pleasing as it is to see the report so well-acknowledged, the danger is that we think: ‘that’s it’. Policy makers need to ensure that action swiftly follows.”

Lord Jim O’Neill Government advisor

UN assembly – the calls for action expressed by Lord O’ Neill have prompted the UK to mirror targets put in place in the USA to halve antibiotic prescribing targets by 2020. But, Lord O’Neill warns: “We will only achieve that if we have diagnostics to support that ambition.”

At the G20 summit in Hangzhou, China, in September, world leaders put AMR on the business agenda for the first time. In another first, at the United Nations General Assembly meeting in New York in October, a concerted ‘one health’ approach to combatting AMR was also adopted. Joining respected alumni such as HIV/AIDS, Ebola and non-communicable diseases, AMR becomes only the

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Test before prescribing QuikRead go CRP ®

C-reactive protein (CRP) testing is recommended by NICE1 for people presenting with symptoms of lower respiratory tract infection in primary care.

See the NICE Medtech innovation briefing2 on QuikRead go for C-reactive protein testing in primary care. #TackleAMR ikread.com

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Distributor in UK & Ireland: Roche Diagnostics Limited burgesshill.cardiacpoc@roche.com 01444 256000 1. NICE Clinical guideline [CG191]. December 2014.

2. www.nice.org.uk/advice/mib78

www.oriondiagnostica.com 10/2016

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Driving improvements

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n 2015, PHE advised NHS England on the development of a Quality Premium for antibiotic use, which incentivises Clinical Commissioning Clinical Commissioning Groups (CCGs) to reduce prescribing of antibiotics by at least 1 per cent from 2013/14 levels.

Investing to save our antibiotic armoury

By Ailsa Colquhoun

Financial incentives to improve antibiotic prescribing have kick-started the pharma industry into vital new antibiotic product development

ENGLAND The rate of Escherichia coli and Klebsiella pneumoniae bloodstream infections increased in England by 15.6% and 20.8% respectively from 2010 to 2014.

15.6% E. coli

20.8%

K. pneumoniae

Rates of Escherichia coli and Klebsiella pneumoniae bloodstream infections in England from 2010 to 2014.

Source: Health Matters Read more on globalhealthaction.co.uk

“It is a fact that the more an antibiotic is used, the more resistance you will see to that antibiotic. That’s why we need to think about how we use antibiotics, as well as when we use them.” That’s the view of Philip Howard, consultant pharmacist in antimicrobials and spokesman for the Royal Pharmaceutical Society.

The term ‘antimicrobial stewardship’ (AMS) is used by healthcare professionals to describe activities to improve cure rates whilst reducing inappropriate antibiotic use and development of resistance.

These activities not only reduce the overall amount of all antibiotics, but especially the strongest and often last-line antibiotics through better focussed treatment based on blood or urine sample results. This tranche of work aims to avoid the situation where an ‘old faithful’ antibiotic becomes so overused that it encourages resistant microbes to develop – and the usefulness of that treatment diminishes – even vanishes – and is then gone for ever.

Although headlines about hospital superbugs suggest that AMR is a hospital-only problem, there is a real need for all parts of the healthcare system to embrace the

Philip Howard Consultant phar­macist in antimicrobials and spokesman for the Royal Phar­maceutical Society

stewardship agenda. To illustrate, Howard points to the 44,000 British people who die each year from sepsis.

Many of the blood infections seen in hospitals start with a common urinary tract infection in the community that can escalate clinically as a result of resistance to the GP-prescribed antibiotic. He says: “Our hospitals are filled to bursting, but if we can prescribe the most effective antibiotic from the start, we could reduce those admissions – keeping patients in their own homes – and keeping more people alive.”

Such is the recognition of the need for AMS that even in today’s cash-strapped NHS there are financial incentives in place across the health service to drive this AMR agenda. For GPs, there are financial incentives that have already resulted in 7 per cent fewer antibiotics prescribed in the last year. In hospitals, the Commissioning for Quality and Innovation (CQUIN) programme

encourages hospital staff to improve the care of the sickest patients with sepsis whilst refining their antibiotic choices through better use of diagnostic testing. CQUINs can contribute up to 2.5 per cent of a hospital’s annual income.

“That’s a large amount of money, and in an NHS where every penny counts, anything that brings money in becomes a priority,” says Howard.

But more crucially, the funding that has followed these work streams has had a number of positive knock-on effects: firstly, it has enabled prescribers to afford newer, but more expensive antibiotics – and this has introduced diversity into prescribers’ antibiotic armamentarium and reduced worries about antibiotic obsolescence. Secondly, increasing demand for new intravenous antibiotics will stimulate pharma industry product development, rekindling interest in what, to date, has been a dwindling field. For the first time in a long time, Howard believes that the microbial conversation has moved from a state of resistance into a plan for resilience. “This is very good news,” he says.

This editorial has been supported with funding from Basilea Pharmaceutica who had no input to the content.

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Translating global promises on a local level

By Kate Sharma

Antimicrobial resistance is an international problem that knows no boundaries.

Tackling the issue requires a willingness to take a global vision for change and translate it into localised action.

When the UN convened in September to discuss antimicrobial resistance (AMR) it sent a message to the world about the global severity of the problem. Only three other health issues, HIV/Aids, non-communicable diseases and Ebola, have been the subject of the general assembly highlevel meetings.

Professor Ramanan Laxminarayan, Director and Senior Fellow at the Centre for Disease Dynamics, Economics & Policy, was part of the UN discussions. He points out that, “meetings and documents by themselves won’t affect change. They merely provide a wave of opportunity. It’s up to us to see how much distance we can get from that wave.”

International collaboration The global commitment for change has inspired international collaboration around a whole range of issues including the innovation of new medicines, data collection, improving surveillance and the development of best practice for the

creating what Laxminarayan describes as a “perfect storm”. Countries such as India, Kenya and China still have a high burden of disease, but as incomes have increased so too has the sale of unregulated antibiotics, perpetuating AMR. Professor Ramanan Laxminarayan Director and senior fellow, Centre for Disease Dynamics, Economics & Policy

use of antibiotics.

The trouble is that, whilst AMR affects both developing and developed countries alike, the issues surrounding the problem differ from region to region. “To change things will take a fundamental shift in the way we think about AMR,” says Laxminarayan, who is also vising Professor at the University of Strathclyde. “This requires a much more localised approach that focuses on the specific challenges of each country.”

A perfect storm Typically, developing countries have experienced the greatest AMR due to the high burden of disease, fewer restrictions on the use of antibiotics and the lack of second line drugs, but the situation is not static.

There are a growing number of countries where rapid economic development is

Local problems need local solutions Country specific practices have also enhanced the problem. In China hospitals make money from the sale of antibiotics, and consequently the country is now one of the world’s highest users of the drugs. In parts of India farmers fatten their animals using antibiotics, to meet the changing diet of the nation. And, in many Western countries, requests from patients for antibiotics to treat simple ailments have resulted in many drugs being prescribed unnecessarily. Global legislation alone can’t tackle specific issues such as these; that requires an ongoing local commitment.

“AMR is going to be a problem forever, so the challenge we have is maintaining the momentum for change,” concludes Laxminarayan.

There certainly is an appetite for that change; it’s up to us not to squander it.

Six strategies needed in national antibiotic policies

1

Reduce the need for antibiotics through improved water, sanitation and immunisation

2

Improve hospital infection control and antibiotic stewardship

3

Change incentives that encourage antibiotic overuse and misuse to incentives that encourage antibiotic stewardship

4

Reduce and eventually phase out subtherapeutic antibiotic use in agriculture

5

Educate health professionals, policy makers and the public on sustainable antibiotic use

6

Ensure the political commitment to meet the threat of antibiotic use

Source: Gelband H, Miller-Petrie M, Pant S, et al. State of the World’s Antibiotics, 2015. Washington DC: Center for Disease Dynamics, Economics and Policy, 2015. http://cddep.org/publications/state_worlds_antibiotics_2015

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Sascha Marschang Policy manager for health systems, EPHA

The need for an international policy response to halt the spread of drug-resistant infections

W

hen antibiotics manufacturers pollute local ecosystems, the environment becomes both a vector of transmission and a reservoir for resistance development. As people and animals come into contact with resistant bacteria, international mobility and trade export them to Europe. What began as an environmental issue thus turns into a healthcare problem as resistant bacteria are received in hospitals and communities. Patients bear the consequences: once superbugs thrive, they are difficult to combat. A post-antibiotic era could complicate many procedures, from childbirth to transplants and chemotherapy.

AMR also threatens drug manufacturers’ survival since their products are worthless if they become ineffective.

Whilst many companies have signed up to the Davos Declaration, others are conspicuously absent. Only a binding legislative approach will work, otherwise some companies will be incentivised to cut corners. Regulators should include environmental criteria into Good Manufacturing Practice.

The environmental dimension must be addressed in the EU’s follow-up Action Plan on AMR taking a One Health approach. EU action must include stricter controls of antibiotic overuse in livestock and environmental standards to stop dumping of active antibiotic waste. The gaps between countries in terms of antibiotics consumption and AMR prevalence must also be closed. The EU has competence to do more.

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Environmental impact of antibiotics production sparks global concerns Concerns over anti-microbial resistance (AMR) have been mounting for years. One major factor is now accepted as being the environmental impact of the pharmaceutical manufacturing process in the two countries which today produce most of the world’s antibiotics – India and China

By Paul Dinsdale

I

n an important milestone, at the G20 meeting in Hangzhou in September 2016, world leaders discussed the serious danger to public health, growth and global economic stability posed by antimicrobial resistance (AMR). More significantly, the issue was addressed at a special United Nations General Assembly High-Level Meeting on AMR later the same month, where global Heads of State for the first time committed to taking a broad, coordinated approach to address the root causes of AMR across multiple sectors.

Ahead of the meeting 13 leading pharmaceutical companies published a ‘Roadmap for Progress on Combating Antimicrobial Resistance’, which contained four commitments starting with a pledge to reduce the environmental impact from the production of antibiotics, including “a review of the companies’ manufacturing and supply chains, and work with stakeholders to establish a common framework for assessing and managing antibiotic discharge”.1 A report published by the Scandinavian investor Nordea earlier this year,2 identified the major public health threat posed by pollution from antibiotics manufacturing plants in India, which is believed to be contributing to soaring drug resistance rates in the country and further afield, it says.

This could have serious implications for global health, as antibiotic resistance genes spread around the world through travel and trade with India. The report gathered evidence from an on-theground investigation in the southern Indian states of Telangana and Andhra Pradesh in early 2016, and

outlines the local impact of drug pollution – including extreme contamination of waterways and agricultural lands – and identifies some of the key players involved. It also showed links between polluting manufacturers and some of the large multinational pharmaceutical companies which they supply, underlining the need to establish and implement strong environmental standards at every stage of the supply chain.

Over the past decade, scientists3 have revealed how dirty production processes and the dumping of inadequately treated antibiotic manufacturing waste in China and India is fuelling the worldwide spread of superbugs, and worsening the impact of the excessive consumption of antibiotics in human medicine and their over-use in livestock farming.

The Nordea report, which was researched by The Changing Markets Foundation and Ecostorm, says that “people living in the vicinity of dirty pharmaceutical manufacturing sites, who are often poor and reliant on subsistence farming, are those whose health is at most immediate risk from the toxic effluents and API-laden waste being deposited in their rivers, lakes, groundwater and fields.

[But] because of the way in which antibiotic manufacturing discharges trigger resistance in bacteria present in the environment, spreading to human pathogens which then travel the world, antibiotic pollution puts everyone at risk, wherever they live.”

In other words, the waste from antibiotic production can affect local populations and people much further afield.

In a stark warning, the first ‘State of the World’s

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Effluent floating on the surface of the Chinna Vagu River, downstream of the Patancheru-Bollarum Industrial Cluster in Hyderabad

Rajiyyapeta, near Visakhpatnam. Pipe discharging apparent effluent onto beach

Antibiotics’ report published by the Washington-based Center for Disease Dynamics, Economics and Policy (CDDEP) in 2015 found that 58,000 newborn babies in India died in 2013 as a result of drug-resistant infections, while Indian drug resistance rates for several major pathogens is also increasing.

In a study published in October, ‘Superbugs in the Supply Chain: How pollution from antibiotics factories in India and China is fuelling the global rise of drug-resistant infections’,4 Changing Markets found that out of 34 sites tested in India, 16 were found to be harbouring bacteria resistant to antibiotics.

“Through our research, we have found evidence that many antibiotics producers are flouting the regulations on environmental pollution, and there could also be corruption of local officials involved,” says Natasha Hurley, campaign manager at Changing Markets.

“The Indian government has recently changed the national pollution control index, by removing criteria relating to health and the environment, a move widely seen as benefiting polluting industries. Although Indian manufacturers are inspected by foreign agencies for their compliance with good manufacturing practice (GMP), these do not extend to environmental pollution, and some big

Natasha Hurley Campaign manager, Changing Markets

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European and US pharma companies are still using some of the worst offenders in their supply chain.

In the light of firm evidence and indications that governments are taking a more proactive approach to tackling AMR, as reflected in the work of the UK government-backed Review on Antimicrobial Resistance, there are positive signs that the issue is being taken much more seriously.

“The AMR Review concluded that environmental pollution from antibiotics factories is a supply chain problem that pharmaceutical companies and their suppliers need to solve together. We now need a more concerted effort by the major US and European pharmaceutical companies to address manufacturing emissions, or else modern medicine as we know it will be put at risk,” says Hurley.

“The pharmaceutical industry now needs to show that it is addressing environmental waste issues in its supply chains, in the same way that the textile industry has begun addressing issues over ‘sweatshop labour’ and conditions in its supplier factories. Any actions should be based on a commitment to increased transparency, making the identity of suppliers public, and setting out measures they are taking to improve their production methods. We

are also calling on major buyers of antibiotics, such as the NHS, to adopt changes to their procurement policies reflecting the environmental impact of pharmaceutical manufacturing. The bottom line is, when it comes to tackling AMR, stamping out environmental pollution from antibiotics production is a low-hanging fruit. One of the most powerful sectors of the economy should more than capable of rising to the challenge.”

(1) http://www.ifpma.org/resource-centre/leading-pharmaceutical-companies-presentindustry-roadmap-to-combat-antimicrobialresistance/ (2) The Changing Markets study for Nordea Asset Management on ‘Impacts of Pharmaceutical Pollution on Communities and Environment in India’, published March 2016.

(3) ‘Effluent from drug manufacturers contains extremely high levels of pharmaceuticals.’

J Larsson, Journal of Hazardous Materials, Volume 148, Issue 3, 30 September 2007, pp. 751–755; and “Pollution from drug manufacturing: review and perspectives”, J Larsson, Philosophical Transactions of The Royal Society B Biological Sciences 369(1656), November 2014.

(4) ‘ Superbugs in the Supply Chain: how pollution from antibiotics factories in India and China is fuelling the global rise in drug-resistant infections’, published by Changing Markets, Oct 2016.