Antimicrobial Resistance - Q4 2019

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CARMEN WILEY, PHD Diagnostics are essential tools in the battle against AMR. » p4

DR HAILEYESUS GETAHUN AMR is one of the greatest threats we face as a global community that has not yet got the attention it deserves. » p2

DR DIANE ASHIRU-OREDOPE Community pharmacists have a lead role in educating patients on antibiotic usage. » p6

Antimicrobial Resistance GLOBALCAUSE.CO.UK

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Why is AMR such an important global issue?

Antimicrobial resistance (AMR) is one of the greatest threats we face as a global community that has not yet got the attention it deserves.

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ntimicrobials are agents that fight d iseases i n hu ma n s, animals and plants. They are critical tools for our continued progress in human medicine and veterinary health this last century.

However, the misuse and overuse of antimicrobials are accelerating the development of drug resistance and they are becoming ineffective.

Alarming levels of drug resistant infections have been reported in countries of all income brackets, resu lting in com mon diseases becoming untreatable and lifesaving medical procedures riskier to perform.

It poses a formidable challenge of reversing a century of progress in tackling diseases, achieving universal healt h coverage and sustainable development goals.

What is the One Health initiative, and how can that be applied when tackling the AMR issue?

The drivers of A M R cut across several sectors; including human and animal health, plants and crops, food production and the

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environment. The ‘One Health’ approach refers to designing and i mplement i ng prog ra m mes, policies, legislation and research in a way that enables these sectors to work together to achieve better public health outcomes.

Implement i ng nat iona l One Health action plans for research and development for diagnostics, vaccines, waste management tools, and safe and effective alternatives t o a nt i m i c r o b i a l s s h o u l d b e t he pr i ma r y respon sibi l it y of national governments.

What are the main barriers to tackling AMR? The challenges of AMR are complex. The transmission of drug resistant infections i s f uel le d by lack of basic access to clean water and sanitation, poor

infection and disease prevention and control in health care facilities and communities.

Additionally, poor access to highquality and affordable medicines, vaccines and diagnostics inflate the crisis. Global understanding of the problem is also a key barrier.

Lack of grass root movements and civil society engagement, and the absence of organised activism and advocacy further dwarf our efforts to tackle antimicrobial resistance.

Who is most vulnerable to the effects of AMR? A M R a f fe c t s ever yone, i n a l l c ou nt r ie s. Wit hout ef fe c t ive a nt i b i o t i c s , i n d i v i d u a l s undergoing routine su rger y or su f fer i ng common illnesses may end up having l i fe-t h reaten ing infections. People are already dying from drug-resistant infections and diseases. Half a m i l l ion T B pat ient s developed drug resistant

The misuse and overuse of antimicrobials are accelerating the development of drug resistance.

WRITTEN BY: DR HAILEYESUS GETAHUN Director of the UN Interagency Coordination on Antimicrobial Resistance, World Health Organization diseases globally in 2018, and only half of them were treated successfully.

As drug resistant infections spread, sustainable food production and global trade will be at risk.

Healthcare expenditures wou ld i nc rea se dramatically. As a result, the World Bank estimated that, by 2030, up to 24 million people – mostly in low-income countries – would be forced into extreme poverty.

– including vaccination, clean water, sanitation and hygiene – will help to control the development and transmission o f i n fe c t io n s , reducing the future need for antimicrobials.

Half a million TB patients developed drug resistant diseases globally in 2018.

Can we help to combat AMR on an individual level?

Supportive individual behaviour of the public and professionals will help to address the misuse and overuse of antimicrobials.

Getting advice from a professional before using antibiotics is the most important intervention that one can do.

Additionally, the utilisation of infection prevention and control

Can we be optimistic about the future of AMR?

We should believe in optimism. We can bend the curve of these crises through intensifying our collective global response with shared vision, innovative and disruptive evidencebased interventions, fixing the broken lines across the One Health spect r um and by avai l ing t he political drive and resources that are required to bring impact at a country level.

The complexit y and urgency of AMR requires comprehensive response and cohesion of actions that put public health at its centre.

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Underuse of antibiotics could be a bigger problem than overuse

Are public-private partnerships the answer to AMR?

WRITTEN BY: THOMAS CUENI Director General, Internation Federation of Pharmaceutical Manufacturers (IFPMA), Chair of the AMR Industry Alliance

WRITTEN BY: DR MANICA BALASEGARAM Executive Director, Global Antibiotic Research and Development Partnership (GARDP)

The 700,000 people around the world, who die each year through antimicrobial resistant (AMR) infections, will have been on the minds of many during this year’s World Antibiotic Awareness Week.

Drug resistance has been identified by the WHO as among the biggest threats to health and development. However, few new antibiotics are being developed, with half of all treatments used today discovered during the 1950s.

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MR is a global health emergency caused by the overuse and misuse of antibiotics. If we do not take action, this alarming figure could rise to as many as 10 million by 2050.

While we are aware of the consequences of drugresistant bacter ia l infections, it is less well known that there are millions of people in low- and middleincome countries (LMICs) who can’t access life-saving a nt i biot ic s . We ignore – at our peril – the problems associated with the failure to provide these life-saving medicines to the world’s poor. Today, it is feared that as many as 5.7m people die in LMICs each year because they cannot get the antibiotics they need.

Facilitating access for half of the world’s population that cannot obtain essential health services is a major challenge. Part of the solution requires getting antibiotics proven to work into the hands of tens of millions of patients in LMICs. These countries must cope with high burdens of infectious diseases and weak health systems and, as a result, struggle to provide basic access to healthcare, including generic antibiotics.

The barriers to better access of antibiotics in LMICs A s t he Cent re for Disease Dynamics, Economics & Policy’s (CDDEP) director, Dr Ramanan L a x m i na ray a n, p oi nte d out in a recent report: “Lack of access to a nt ibiot ic s k i l l s more people currently than does antibiotic resistance, but we have not had a good handle on why these barriers are created.” And this crisis has been with us for decades.

CDDEP found that of 21 new antibiotics entering markets bet ween 1999 and 2014, fewer than five were registered in most countries in sub-Saharan Africa.

Health facilities in many LMICs are substandard and lack properly trained staff for administering antibiotics. In Uganda, 10 to 54% of health staff posts are unfilled because of poor pay, high stress, lack of resources, and poor management.

As a result, there is inadequate staff available in wards to administer medicines. Subsequently patients miss antibiotic doses, a nd publ ic nu rses somet i mes request compensation for administering medicines.

5.7 million people die in LMICs each year because they cannot get the antibiotics they need.

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India has a deficit of 600,000 doctors compounded by a shortage of two million nurses. Globally, 800m people spend at least 10% of their budget on health, pushing 100m of these each year into extreme poverty – forced to live on $2 a day.

High price s of tre atme nt in LMICs In the case of antibiotics, one thing is clear: price of treatments should not be the reason preventing people from accessing them, since 90% of current antibiotics are ‘affordable’ generics. However, lower costs of generics are not always passed on to consumers, who often pay for the antibiotics from their own pockets.

In India, public sector proc urement pr ices of cer tain o l d e r, o f f- p a t e n t a n t i b i o t i c s (including amoxicillin, ampicillin s u s p en s ion, dox yc ycl i ne, a nd erythromycin) were higher than for newer antibiotics.

As recommended in the Chatham Hou se Rev iew of P rog re s s on A nt i m icrobia l Resista nce, t he problem of access to antibiotics can be remedied by providing quality hea lt hcare to a l l, and mov ing towards universal health coverage in LMICs, as it will address the problems of both adequate access to antibiotics and restricting over-thecounter sales.

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hile drug resistance occurs nat u ra l ly over t i me, a number of factors have increased resistance in bacteria. These include overuse and misuse of antibiotics in humans and animals, as well as in food production, poor infection prevention and control, and lack of affordable access to medicines. The challenge requires a wider solution than just developing new drugs if we are to prevent the estimated 700,000 deaths worldwide every year as a result of AMR. T ac k l i n g t h i s g lob a l p ubl ic health challenge cannot be solved by one cou nt r y, orga n isat ion, stakeholder or actor alone; this can only be addressed through a global, multi-sectorial approach based on partnerships that bring actors who complement each other together.

A public–private partnership approach Making new treatments available for every person who needs them requires a partnership approach with both the public and private sectors. The private sector brings sig n ificant in novat ion and experience in the development a nd del iver y of t reat ment s.

However, a purely market-driven approach has not produced enough new antibitotics.

P ublic sector involvement is needed to identify public health needs, set pr ior it ies, injec t funding and re-shape incentives for t he pr ivate sector. P ubl icprivate partnerships can leverage t he b e s t of b ot h s e c tor s a nd provide a transparent vehicle for collaboration, focused on achieving a mutually beneficial objective to make infections treatable for everyone, everywhere.

Accelerating new treatments I n fac t, t he Globa l A nt ibiot ic Research a nd Development Partnership (GARDP) was created to address this global challenge, and is actively driving R&D into treatments in late-stage clinical MEDIAPLANET

development that target priority pathogens identified by the World Health Organization, the needs of priority diseases and populations, while promoting responsible use and affordability to all in need – an area where few others are active.

After three years, GARDP has built a pipeline to address infections in children, hospitalised adults and sexually-transmitted infections.

While t he burden is highest among v ulnerable populations – women, children, the elderly, i m mu no - c omprom i s e d p e ople and those in countries with weak health systems – AMR can affect anyone, of any age in any country.

Focusing on children is important and reflects the fact that, while significant progress has been made in recent years to improve child health globally, death in newborns represents 44% of all deaths in children under the age of five.

In Europe – the richest part of the world – research shows drugresistant infections are responsible for an estimated 2,300 disabilityadjusted-life-years per 100,000 people every year. And the burden, which is highest in infants under one, has increased significantly since 2007. Of further concern is the estimated 214,000 deaths in newborns attributable to drugresistant infections.

What needs to happen?

S evera l c ou nt r ie s a re a l re ady showing strong leadership and financial commitment towards addressing this global health and development crisis by supporting initiatives that have been launched to reinvigorate the antibiotic R&D pipeline over the last few years.

Despite this, more can and must be done to significantly scale-up our efforts to address the magnitude of the public health challenges we face today and ensure these efforts sit within a public-health focused R&D framework.

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Fighting AMR with machine learning and immunebased diagnostics CO AUTHORS: DR KFIR OVED, DR TANYA GOTTLIEB

Why clinical laboratory testing is key to fighting antibiotic resistance CARMEN L. WILEY, PHD President, American Association for Clinical Chemistry

Clinical laboratory experts are using innovative new tests to provide doctors with the insights they need to curb unnecessary antibiotic use.

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f I asked you what the solution is to the antibiotic resistance crisis, the first thing you might think of is creating new drugs that kill resistant microbes. What you might not realise, though, is that new clinical laboratory tests for infectious diseases are equally important. These tests – and the scientists who develop and perform them – are crucial to preventing antibiotic misuse, which is one of the major drivers of this global health threat.

Overuse of antibiotics – often with patient wellbeing at heart Antibiotics are indispensable for treating bacterial infections like strep throat or pneumonia, but they don’t work – and shouldn’t be used – for viral illnesses such as the common cold or flu. In the past, however, traditional culture-based tests could take several days to determine whether a patient had a bacterial infection and which antibiotic would treat it effectively. Doctors couldn’t postpone treatment for this long, especially in cases where a delay was potentially life threatening. So instead, they would often prescribe antibiotics automatically while waiting for test results to come in.

This practice had patients’ best interests at heart, but unfortunately contributed to rampant antibiotic overuse, which, in turn, has fueled the spread of resistance to these drugs.

Improved testing to reduce default prescribing To help solve this problem, the scientists who work in clinical laboratories have developed new tests that greatly reduce the time it takes to diagnose infectious diseases. For simpler cases, such as when a patient has a respiratory infection, clinical laboratory experts have created tests that identify bacteria and viruses through their genetic material, and that return results in hours or even in minutes.

For more complex cases, such as surgical infections, clinical laboratory experts have also modified mass spectrometry (a powerful molecular analysis technique originally designed for research) to create tests that rapidly identify up to nearly 200 different microorganisms at a time.

Most of these new tests are less than a decade old, but thanks to their accuracy and speedy turnaround times, they are already essential tools in the battle against antibiotic resistance. Using these tests, clinical laboratory experts can now promptly provide the information that healthcare teams need in order to decide whether antibiotics are the right treatment for a patient. This will help limit unnecessary antibiotic use, while ensuring that antibiotics continue to work for the patients whose lives depend on them.

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DR ERAN EDEN Co-Founder and CEO, MeMed Ltd.

A new platform that measures the body’s immune-protein response, coupled with machine learning, can accurately distinguish between bacterial and viral infections within minutes - an effective tool in the fight against AMR. The Challenge: Is it a bacterial or viral infection? To treat or not to treat with antibiotics?

When a patient presents with fever, in many cases, the question comes down to whether it is a bacterial or viral infection, and if to treat, or not to treat, with antibiotics.

Making this diagnosis can be challenging as bacterial and viral infections are frequently clinically indistinguishable.

Tools for detecting pathogens are used to aid the diagnosis, but actionability is often constrained by their inherent limitations: • Reliance on pathogen sampling, which can be difficult when site of infection is inaccessible or unknown • Inability to distinguish between detection of a pathogen versus coloniser • L imited performance against emerging pathogens As a result, the disease causing pathogen is not clearly identified in as many as two out of three patients w it h acute infection, even when applying cutting edge microbiological tools.1–3 New diagnostic paradigm: decoding the immune response with machine learning A c omple m e nt a r y d i a g n o s t ic paradigm has emerged in recent years that overcomes the limitations of d i re c t pat hogen dete c t ion, namely har nessing t he body ’s immune-response to infection. It has several advantages:

• N o requirement to access the i n fe c t ion site b e c au s e t he i m mu ne s ystem c i rc u lates throughout the body • C ap a b i l it y t o d i s t i n g u i s h between pathogen and coloniser, a s t he i m mu ne s y s tem i s primarily triggered by diseasecausing agents • R o b u s t n e s s t o e v o l v i n g pat hogen s, as t he im mu ne system is triggered by multiple pathogen features Currently, individual host-proteins – such as procalcitonin and C-reactive protei n – a re used to suppor t infection management. However, as single biomarkers, they are often insufficiently accurate due to patient-to-patient variability.

Advancements in host-response profiling and machine learning algorithms have opened the way to a new generation of diagnostics that involve computational integration of multiple biomarkers.

Today, there are several such tools in development. Only one diagnostic has been cleared (currently in Europe) that combines the hostresponse with machine learning to distinguish between bacterial and viral infections.

It s development i nclude d screening over 100,000 biomarker combinations. The best performing c ombi n at ion c omput at ion a l ly integrates three circulating hostproteins: TRAIL/IP-10/CRP.1 This signature has since been validated in multiple double-blind international studies enrolling thousands of patients and has shown superiority to routine tests.2–6

Reduction to practice: measuring the immune-protein signature within minutes to fight AMR Hav i n g a n acc u rate i m mu ne s i g n at u re i s not enou g h . F or example, although already used to guide treatment of >10,000 patients in Europe, the impact of the TRAIL/ IP-10/CR P sig nat ure measured using an ELISA platform has been con st ra i ned by t he laborator y burden and prolonged turnaround time (two hours).

Broad impact of im munesignatures requires platforms that can measure multiple biomarkers, across a w ide dy nam ic range, quantitatively, rapidly (within 15 minutes), across different clinical settings, in an easy to use manner.

Meeting these requirements is readily achievable for circulating host-proteins and will likely take longer for other host biomarker families (e.g. intracellular proteins, RNAs, metabolites).

Several platforms for measuring host-protein sig nat ures are in development, including one to measure TRAIL/IP-10/CRP in under 15 minutes.

Regulatory clearance of these products w ill pave the way to reducing diagnostic uncertainty when and where needed, improving patient management and reducing antibiotic misuse, ultimately helping the global fight against AMR.

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Treating infections and preserving the gains of modern medicine will require stewardship and investment As an infectious diseases physician, I have come to dread seeing a patient’s condition worsen – and even become life-threatening – due to an infection that would have once been simple to treat.

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nfortunately, the rising tide of antibiotic resistance, coupled with insufficient re s e a rc h a nd development of new antibiotics, is making this devastating scenario more frequent.

Not on ly does t h is mea n t hat once easily treatable infections can now be fatal, but many of the life-saving medical advances that we’ve come to take for granted — cancer chemotherapy, organ and bone marrow transplants, joint replacements and other surgeries — m ay b e c ome i mp o s s ible to perform safely. These procedures increase infection risk but have been made safe by antibiotics. Now we are seeing increasing numbers of patients who can beat cancer or successfully receive a new kidney, liver, hip or knee, only to die from an infection that is resistant to antibiotics. How did we get here?

And, perhaps more importantly, how can we ensure that we do not lose antibiotics—and the medical advances they enable—entirely? The solution is complex, but attainable and necessary.

Appropriate use of antibiotics Overuse and misuse of antibiotics drives the development of antibiotic resistance. This means that the more we use antibiotics, the less effective they become over time. We need coordinated interventions in hospitals, doctors’ offices and other healthcare settings to ensure that antibiotics are used appropriately.

Infectious diseases physicians lead a nt ibiot ic stewa rdsh ip programmes—efforts whose very purpose is to promote optimal antibiotic use.

Ample data demonstrates that

stewardship programmes reduce inappropriate antibiotic use and i mp rove p at ie nt o utc ome s — meaning that patients are cured and released from the hospital more quickly and are less likely to suffer from negative side effects associated with inappropriate antibiotic use.

The federal government needs to invest in stewardship programmes and in the expert workforce needed to make them work.

DR THOMAS FILE, JR, FIDSA President, Infectious Diseases Society of America has largely abandoned antibiotics b e c au s e t he s e d r u g s a r e no t profitable. Typically taken for a short duration and held in reserve to protect their usefulness, antibiotics do not yield a quick return on the investment required to develop them. The federal government must step in to ensure that the antibiotic market does not collapse, rever s i n g de c ade s of me d ic a l

progress and leaving physicians a nd pat ient s w it hout t hese life-saving medicines.

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Action needed from policymakers Stewardship alone will not solve this problem. Even necessary and appropriate antibiotic use will cause resistance to develop, albeit at a slower rate. We need to invest in the discovery and development of new antibiotics.

The pharmaceutical industr y

Combatting antimicrobial resistance: molecular diagnostics holds the key Antibiotic resistant bacteria are one of the major threats to the global healthcare system. Some have commented that it is a more immediate threat to us than global warming.

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U K i ndependent rev iew e s t i m ate d t h at , u n le s s effective action is taken, drug-resistant strains of certain bacterial infections will claim 10 million lives each year by 2050.

This would be a horrific and tragic loss of life. The unchecked spread of infectious diseases was also predicted to result in an economic cost of 100 trillion USD over the next 35 years1. “ The threat of antimicrobial resistance (AMR) and infectious diseases is rising. We will need all branches of the global healthcare system to take responsibility for their approach to antibiotics and work together to sustain them for f ut u re use – t h is i ncludes clinicians, providers, companies and patients alike,” says Tuomas Tenkanen, CEO of Mobidiag. “Even before treating conditions related to A MR, it is fundamental that we become smarter at identifying MEDIAPLANET

antibiotic resistant bacteria – and their sensitivity to antibiotics – using molecular diagnostics. Many mole c u la r d iag nost ic s ystem s available today can be complicated and expensive to use,” he continued.

Highly versatile platforms enabling broad application of molecular diagnostics At Mobidiag our mission is to develop innovative molecular solutions to address the challenges of AMR and infectious diseases by providing diagnostic tools that can rapidly, accurately and affordably detect both pathogens and antibiotic resistances to guide treatment protocols and avoid the misuse of antibiotics.

To address this challenge, we have developed two highly versatile, combined solutions, for affordable and differentiated AMR testing. The first is an advanced, cartridge-based multiplex PCR system providing

highly sensitive results on demand; and the second a higher throughput diagnostic platform allowing for automated, mid to high-volume lab-based routine testing. Together, these platforms meet the differing needs of customers in multiple healthcare settings.

Unlocking the potential of molecular diagnostics to address the global challenge of antimicrobial resistance Beta-lactams are by far the most used antibiotics worldwide, and i nclude ca rbapenem s wh ich are the most effective against Gram-positive and Gram-negative bacteria. However, during the last decade, Gram-negative bacilli (in par t ic u lar Enterobac ter iaceae) with a decreased susceptibility to c a rbapenem s have been increasingly reported worldwide.

There is also a growing resistance

TUOMAS TENKANEN CEO, Mobidiag to ‘last resort’ antibiotics such as vancomycin and colistin. With the aforementioned developments in molecular diagnostics, new tests offer unique solutions to detect main CPO2, colistin and vancomycin resistance markers.

I n 2 0 1 7, W H O d e s i g n a t e d clarithromycin-resistant Helicobacter pylori a high priority for a nt ibiot ic resea rch a nd development. There is now a noninvasive qua l itat ive mu lt iplex real-time PCR test for identifying both H. pylori and its clarithromycin resistance directly from stool and gastric biopsies.

Finally, sepsis is a global health care issue and continues to be the leading cause of death from infection. A M R can jeopardise clinical management of sepsis b e c au s e e mp i r ic a l a nt i b io t ic t r e at m e nt i s of t e n r e q u i r e d .

There is now work ongoing to develop a revolutionary assay for

quick detection of sepsis directly from blood.

Mobidiag have developed two highly versatile combined solutions for affordable and differentiated AMR testing: Novodiag®, an advanced, cartridge-based multiplex PCR system providing highly sensitive results on demand; and Amplidiag® a higher throughout diagnostic platform allowing for automated, mid to high-volume lab-based routine testing.

Sources: 1) Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations, The Review on Antimicrobial Resistance Chaired by Jim O’Neill, December 2014 2) CPO: Carbapenemase producing organisms including the family of Enterobacteriaceae, Acinetobacters and Pseudomonas

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We are seeing an emergence of antifungal resistance PROFESSOR MAURIZIO SANGUINETTI President-Elect and Secretary General, European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

It was only very recently that the World Health Organization’s global antimicrobial resistance surveillance system has considered emergence of resistance among fungal pathogens1.

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his settled lack of interest is primarily because fungal diseases are generally not transmissible among humans.

Nevertheless, fungal pathogens such as Candida and Aspergillus represent a major cause of life-threatening invasive diseases, especially in patients with impaired immunity2.

More people die from fungal i n fe c t ion s e ach ye a r t ha n by m a l a r i a or t ub erc u lo s i s . The emergence of resistance to the most commonly used classes of drugs — triazoles, echinocandins and polyenes, is a growing public health threat that greatly hampers the patient management3.

Emergence of multidrugresistant species While the antifungal resistance to a ny one d r u g- c l a s s l i m it s t he t herapy, due to paucit y of therapeutic options, multidrug resistance can definitely eliminate these options.

Azole resistance among Candida and Aspergillus species has become a substantial cause for concern, fol lowed by echinocandin and multidrug resistance among some Candida species.

A not her i mp or t a nt C a nd ida species with a multidrug-resistant phenotype is Candida auris 4, which emerged in clonal outbreaks within Indian healthcare facilities some years ago.

Si nce t hen, t h i s mu lt id r ugresistant species has emerged worldw ide a s a hea lt hc a re associated fungus causing invasive infections with high rates of clinical treatment failure.

Poor infection control may increase chances of transmission A recent international study found that, overall, 41% of the isolates from 54 patients with C. auris infection were resistant to two antifungal c l a s s e s (mu lt id r u g-r e s i s t a nt) and 4% were resistant to three classes (triazoles, echinocandins, and polyenes)5.

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A lt hough t he d r ivers of t he C . aur is emergence remain unk now n, extensive empirical f luconazole usage and poor infection control may promote eas y t ra n sm ission of C . au r is among patients.

The emergence of multidrugresistant C. auris recalls the need for enhanced sur veillance and novel therapeutic agents. These m ay i nc lu d e n e w a nt i f u n g a l agents, repurposed existing agents, analogues of existing antifungal agents, and combination therapies.

In this context, we must invest in the development and enhancement of d i a g no s t ic pl at for m s t h at c a n r ap i d l y d e t e c t r e s i s t a nt fungal diseases6.

Stewardship should include diagnostics, drug monitoring and intervention As effective antifungal stewardship i s e s s e nt i a l t o c o nt r o l d r u g resistance, it should incorporate rapid fungal diagnostics, therapeutic dr ug mon itor ing, and cl in ica l inter vention teams to preser ve drug effectiveness.

L o ok i n g a he ad, m ic robiome research and whole-genome sequencing analysis w il l offer tools for enhancing our capacity to recognise drug resistance and prov iding effective antif unga l stewardship in the next years6.

Finally, if better provision of fungal diagnostic testing may be a means of curtailing antibacterial u s a g e 7, i t w i l l b e o b j e c t o f further investigation.

Sources: 1. WHO. Meeting on global surveillance of AMR in invasive Candida infections, 24 April 2018, Madrid, Spain. http://who.int/glass/events/ AMR-in-invasive-candida-infections-meeting/en/ (accessed Oct 31, 2018).

2. Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR. Fungi that infect humans. Microbiol Spectr. 2017;5(3).

3. Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017;17:e383-e392.

4. Meis JF, Chowdhary A. Candida auris: a global fungal public health threat. Lancet Infect Dis. 2018 Oct 4.

5. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis. 2017;64(2):134-140.

6. McCarthy MW, Denning DW, Walsh TJ. Future research priorities in fungal resistance. J Infect Dis. 2017;216:S484-S492.

7. Denning DW, Perlin DS, Muldoon EG, Colombo AL, Chakrabarti A, Richardson MD, Sorrell TC. Delivering on antimicrobial resistance agenda not possible without improving fungal diagnostic capabilities.

Emerg Infect Dis. 2017;23:177-183.

Community pharmacy teams are key in antimicrobial stewardship The primary goal for antimicrobial stewardship is optimising outcomes for patients while minimising unintended consequences.

DR DIANE ASHIRU-OREDOPE Lead Pharmacist, HCAI and AMR Division, Public Health England

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t is also an approach that aims to reduce the transmission of i n fe c t ion s a nd e duc ate healthcare professionals, patients and the public.

Alongside infection prevention and control, making better use of data and improved diagnostics, antimicrobial stewardship i s a n es sent ia l comp onent of tackling AMR. Community pharmacy teams have an important contribution and lead role in educating patients and customers on why antibiotics are only prescribed and used when needed, as well as how to effectively manage self-limiting infections.

Without antibiotics, there are many conditions that cannot be treated As professionals, we know that without antibiotics healthcare would take a huge step backwards.

Without them we can’t treat chest infections and UTIs, or ensure that our amazing advancements and lifesaving treatments like transplants, chemotherapy and even childbirth remain safe.

Evidence from studies combined together showed that when patients take antibiotics for self-limiting infections where they are unlikely to be effective, we are increasing unintended consequences for those patients. For example, the common cold and flu symptoms are most likely due to viral infections for which antibiotics have no effect.

Both common cold and f lu can usually be treated through selfmanagement without the need

Patients should be encouraged to return any unused antimicrobials to the pharmacy, and not to dispose of them at home or save them for later or share with others.” to see a doctor, with symptoms starting to relieve after around one week.

Community pharmacy teams help with self-management and self-care Community pharmacy teams are part of the fabric of society, and our teams across the country, who see more than one million people each day, can carry out antimicrobial stewardship interventions that can be contributed in the fight against antimicrobial resistance.

When a customer visits a pharmacy with a prescription, there are usually three stages to the prescription’s j o u r ne y a nd t he r e for e t h r e e opportunities to implement best antimicrobial stewardship practice.

At hand-in stage, pharmacists can collect information that will later be used to check the antibiotic is appropriate for the patient – and check their infection – as well as help personalise information for the patient. This includes finding out what i n fec t ion t he ant ibiot ics are f o r, l e a r n i n g

the patient history and what the patient already knows about how to take the antibiotics they have been prescribed.

Advising patients against storing or sharing antibiotics At the hand-out stage, pharmacists should provide advice about the antibiotics dispensed. This includes taking them at regular intervals as prescribed, whether they need to be taken with or without food, and how long they have been prescribed the antibiotics for.

Patients should be encouraged to return any unused antimicrobials to the pharmacy, and not to dispose of them at home or save them for later or share with others.

Pharmacists should also advise p at ient s i f a lc ohol shou ld b e avoided — some pat ients have misconceptions that alcohol should be avoided with all antibiotics, and sometimes this prevents them from taking their medication.

Antibiotics are not always the solution Research shows that inappropriate prescribing is, in par t, due to patients expecting – or demanding – antibiotics without understanding that they may not be effective for their illness. There is an opportunity here for pharmacists to help tackle t his lack of understanding by giving advice when customers visit feeling unwell.

Key information is available that can be used by pharmacy teams when advising patients with self l i m it i n g i n fe c t ion s who s e ek support from pharmacy teams.

This includes usual duration of common infections, which helps to reassure the patient, self care advice to share with the patient, and possible signs of serious illness that should be assessed urgently by a medical team.

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Finding solutions to antibiotic overuse

CONTRIBUTOR: DR VERENA GATNER General Practitioner, Switzerland

Antibiotic resistance is the climate crisis of medicine — the man-made depletion of a vital medical resource due to rampant worldwide overuse.

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orwegian researcher, Dag Berild, has been studying rational antibiotic use for 30 years and explains how C-reactive protein point-of-care testing, using devices is a simple step doctors can take to help curb this coming crisis.

Antibiotics are among the most v a l u a ble c l a s s o f d r u g s e ve r discovered. They save countless lives every year and make many ot her procedures — such as transplantation, cancer therapy and surgery with prostheses — possible.

H o w e v e r, d u e t o r a m p a n t worldwide overuse, there is a danger of losing this essential medical resource soon.

“Un for t unately, t he world is he ade d i nto a p o s t-a nt ibiot ic era because of t he over use of a nt ibiot ics,” 1 says Dag B er i ld, C o n s u l t a nt a n d P r o fe s s o r o f Infectious Medicine at the University of Oslo and Oslo Metropolitan University. “If this continues, we will not have antibiotics in maybe 20 or 30 years. The more you use it, the more you lose it.”1

We must stop pre scribing antibiotics for viral infections The primary problem, say Berild and other experts, is the practice of prescribing antibiotics for selflimiting viral illnesses — such as respiratory tract infections — rather than limiting their use to treating severe bacterial infections and disease.

“The most common reason for prescribing antibiotics in primary care is respiratory tract infections,”1 says Berild. “ They account for mor e t h a n 5 0 % of a nt i b io t ic prescriptions, both in hospital and in general practice.”1 In a large portion of those cases, the infection is viral and will not respond to antibiotics. The patient will bear the burden of cost and may suffer side effects. The repeated overuse contributes to antibiotic resistance in their region.

“Countries that have a higher prescr ibing rate of antibiotics also have higher antimicrobial resistance,”2 says Dr Verena Gantner, a general practitioner in Muri, Switzerland. “In Central Asia, we got used to seeing doctors prescribe antibiotics that were not needed

This is not just a medical issue, it’s an ethical one...

Our generation misues antibiotics and created this problem.”

— even more than in Europe. And patients pay for that.”2 L ord Ji m O’ Nei l l, a for mer chair man of Goldman Sachs and professor of econom ics at t he Un iversit y of Manchester, led the Review on Antimicrobial Resistance (AMR) on behalf of the British government.

O’Neil’s researchers concluded that if we don’t undertake big policy initiatives, by 2050 there could be 10 million people around the world dying from AMR-related illnesses.

Among the most important needs is rapid and affordable diagnostics.3

Sources: 1. https://alere.wistia.com/medias/hv508ngwpj 2. https://alere.wistia.com/medias/ey0c7ub7xg 4. Cals, JW, et al.BMJ. 009;338(51):137 5. Little P, et al. The Lancet 2013; 382(9899):1175-1182 MEDIAPLANET

CONTRIBUTOR: DAG BERILD Consultant and Professor of Infectious Medicine, Metropolitan University

Improving diagnostics with CRP point-of-care testing Berild points out that rapid and affordable diagnostics do currently exist. “We use CRP point-of-care testing for respiratory infections in Norway,”1 says Berild. “This helps us discriminate between serious bacterial infections that need to be treated with antibiotics and selflimiting disease.”1 CRP uses a simple finger stick to test a patient’s blood for C-reactive p r o t e i n (C R P), a m a r k e r fo r inflammation and infection that can reduce diagnostic uncertainty and over-prescription of antibiotics in patients with viral infections.

A high CRP result indicates a severe bacterial infection where antibiotic treatment would likely be beneficial, but a low value indicates a viral or self-limiting infection that would be better treated by other means.

“C R P i s a ver y i mpor t a nt biomarker,”2 says Dr Gantner. “The benefit of CRP point-of-care testing is that I can take blood from only a fingertip and have results in about three minutes. Then I can show the value to my patients and they

are reassured they have only a viral infection.”2 Evidence shows that CRP point-ofcare testing works on a broader level.

Two large studies in six European countries found that combining CRP point-of-care testing and enhanced communication skills of healthcare professionals resulted in a relative reduction of antibiotic prescribing by more than 60%.4, 5 “Very few new antibiotics have been developed in the past 30 years so, it is crucial that we preserve t he one s we c u r rent ly have” 1 says Berild.

“This is not just a medical issue, it’s an ethical one,”1 says Berild. “Our generation misused antibiotics and created this problem, so when our children and grandchildren need them, there will be no effective ones left.”1

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3.https://antimicrobialresistancefighters.org/stories/story-lord-jim-o-neill

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