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WHO to develop global plan to tackle antimicrobial resistance

International pressure to create a global plan mounted following a recent WHO report on antimicrobial resistance surveillance

The World Health Organization (WHO) will prepare a draft global plan to tackle the growing problem of antimicrobial resistance, it was announced at the World Health Assembly in Geneva, Switzerland, last month (24 May 2014).

The resolution urges countries to strengthen their drug management systems, to support research to extend the lifespan of existing drugs, and to encourage the development of new diagnostics and treatment options. Once the draft plan is complete, it will be presented to member states for approval at the World Health Assembly in May 2015.

International pressure to create the plan mounted following the publication last month of a WHO report on antimicrobial resistance (AMR) surveillance. The report identified resistance in seven different bacteria responsible for common and serious infections, including pneumonia, sepsis, diarrhoea, urinary tract infections and gonorrhoea.

The plan is to coordinate international efforts to reduce the use of antimicrobials, integrate prevention of antimicrobial resistance for humans and animals, improve prevention and control of infection through sanitary measures and vaccination, enhance global AMR awareness, and promote access to quality medicines and healthcare.

Margaret Chan, director-general of the WHO, said: “AMR is making modern medicine useless.” Between 1983 and 1992, US authorities approved 30 new antibiotics, but this fell to just seven between 2003 and 2012, because drug companies have too few incentives and face too many regulatory barriers.

There have been no new classes of antibiotics for 25 years, and with no new antibiotics in development, “the pipeline is anaemic”, says Katy Athersuch, a policy adviser for the humanitarian charity Médecins Sans Frontières. She believes that society can no longer rely on the traditional research and development model, and that “we need to develop a new incentive scheme to spur innovation of new diagnostic tools as well as medicines”.

On a par with climate change

A few days before the resolution was passed, two experts wrote in the journal Nature that a “powerful” international panel is needed to tackle the growing threat from AMR.

In many ways, AMR is similar to climate change, they argued. “Both are processes operating on a global scale for which humans are largely responsible. In antimicrobial resistance, as in climate change, the practices of one country affect many others,” wrote Mark Woolhouse, an epidemiologist at the University of Edinburgh, UK, and Jeremy Farrar, director of the Wellcome Trust.

Their proposed intergovernmental panel on antimicrobial resistance (IPAMR) would be similar to the Intergovernmental Panel on Climate Change (IPCC), which was created in 1988, and which they believe is “arguably the most successful attempt in history to empower scientific consensus to inform global policy and practice”.

The IPAMR would encourage the implementation of policies to prevent the loss of effective drugs to resistance, and promote the development of alternatives. They stress that the panel must be trusted and “free of vested interests”, and should include a broad range of experts. It would also need financial, industrial and political support from governments and agencies, including the WHO, the World Organisation for Animal Health, and the World Trade Organization, as well as industry.

In June, the WHO will host a global conference at The Hague in the Netherlands on antibiotic resistance with the theme “joining forces for future health”. The objective will be to accelerate political commitment in the fight against AMR and contribute to the global action plan.

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11138821

Readers' comments (3)

  • Thank you for this report. I am very interested to hear about the work on Antimicrobial Resistance so to hear about the June Global conference is great to know.

    Do you have any more details or could refer me to where I can register to attend if it is possible to do so.

    Kind Regards

    David Preece

    The European Association of Hospital Pharmacists  

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  • Thanks for your comment. Here's the conference website:

    Best wishes,
    Dawn Connelly

    PJ Online team

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  • Richard Schmidt

    The announcement that NESTA is to fund a £10 million prize‚ the Longitude Prize 2014‚ to "speed up progress towards meeting the challenge of resistance to antibiotics by stimulating invention and innovation‚ especially 'out of the box' thinking" has to be applauded. Bizarrely, NESTA [echoing Katy Athersuch of Medécins Sans Frontières; see article above] then defines the challenge more precisely in terms of a need "to create a cheap, accurate, rapid and easy-to-use point of care test kit for bacterial infections." [1] This is not what I would call "out of the box" thinking ... but perhaps I'm missing something?

    Along with [probably] every other community pharmacist in the land, as I hand out their prescribed antibiotics, I slavishly seek assurance from patients that they do understand the instructions they should have been given by their GP to take the prescribed dose and to finish the course. But why do I/we do this? The answer to this question, if not provided earlier, was provided in May 2006 on the NeLI [National Electronic Library of Infection] Antimicrobial Resistance Website: "The longer bacteria survive the more likely they are to become resistant to the drug. If you stop taking antibiotics before they & your immune system have eliminated the bacteria the remaining bacteria will multiply rapidly." [2]

    So, to paraphrase NeLI, the likelihood of resistance emerging increases the longer a micro-organism survives exposure to an antibiotic. And yes, that makes sense. But, does it follow that a failure to take or use the full course of an antibiotic will make emergence of resistance LESS likely? And will the availability of a test kit, this presumably being a test kit capable of aiding the selection of an appropriate antibiotic, help reduce the development of resistance? Of this I'm not so sure.

    On the basis that a bacterial infection is unlikely ever to be monoclonal (because it takes more than one bacterium and probably nearer 100 or even 1000 to initiate an infection), it follows that amongst that population of infecting micro-organisms there will [probably] always be some individual organisms that will be naturally resistant to the chosen antibiotic regardless of whether or not there has been previous exposure to that antibiotic. We do not need to postulate that resistance to an antibiotic emerges as a result of random genetic mutation AFTER first exposure to the antibiotic. So, logically, by decreasing the population of those that are not resistant, antibiotic use will actively select for resistant individuals. Therefore, I would argue that the longer the course of an antibiotic, the more likely it is that a strain resistant to that antibiotic will clonally expand ... unless it is cleared by another process, e.g by the immune system.

    What actually matters is the extent to which clonal expansion of the resistant strain occurs and whether these resistant organisms then escape into the environment. And we should not overlook the fact that when a human is treated with an antibiotic, it is not only the infecting micro-organism(s) that is/are exposed to the antibiotic but also all other members of the ecological community that is the patient's microbiome. Amongst these organisms too there will be clonal expansion of resistant strains and the risk of escape into the environment. Staphylococcus aureus is a case in point. This is a potentially pathogenic but normally harmless commensal organism found on the skin. Strains of this organism (e.g. "MRSA") now show resistance to a wide variety of antibiotics. Antibiotic resistance in gut bacteria will arise in a similar fashion. No test kit could ever be developed that could change this because this phenomenon occurs as an inevitable consequence of the use of ANY antibiotic that distributes itself to the skin and/or the gut after administration.

    Whilst NeLI does acknowledge that the immune system has a role to play, discussions of antibiotic resistance in the context of pharmacy practice seem never to contemplate the role of the patient's own immune system. Unless a patient is immunocompromised or is taking an immunosuppressant, e.g. a DMARD ("disease modifying anti-rheumatic drug"), the antibiotic and the immune system normally work TOGETHER to clear an infection. And fundamental to this is our ability to mount an inflammatory response involving phagocytic white blood cells. These phagocytes kill bacteria (if they can get to them) and they then work to clear the battlefield.

    Inflammation causes pain. Pain causes inflammation. In a patient with an infection, inflammation and pain are signs that the immune system is fighting the infection. But the common experience of every community pharmacist will be that patients prescribed an antibiotic will often also be prescribed an opioid or anti-inflammatory pain killer or will use a pain killer purchased over the counter in the pharmacy or elsewhere in the irrational belief (on the part of both the prescriber and the patient) that pain and inflammation have to be treated symptomatically whilst the antibiotic does its work. This is like going into battle with one arm tied behind your back and, I would say, helps resistance to emerge.

    Pain killers are known to interfere with healing; non-steroidal anti-inflammatory drugs (NSAIDs) can not only mask the signs of an infection but also interfere with the ability of the immune system to clear an infection. A recently published study of the impact of NSAIDs (and smoking) on infection rates and healing of traumatic long-bone fractures supports this view. [3] I could also cite many earlier studies demonstrating this. So, should we not be maximising the contribution made by our immune system to the fight against infecting organisms by not reaching so quickly for pain killers and accepting that "you have to hurt to heal"?

    As is well established in fields as diverse as cancer chemotherapy and fungicide use in horticulture, the more specific the mechanism of action of a chemotherapeutic agent, the more likely it is that resistance will emerge. Conversely, the greater the number of cellular processes that are targeted by therapy, the less likely it is that resistance will emerge. That is why multi-drug chemotherapy regimens have been developed for the treatment of cancers. This is why little or no resistance has ever emerged to old-fashioned "dirty" antifungals such as copper salts, sulfur and mercurials that affect a multitude of processes in the target organism.

    Typically, modern drug discovery strategy aims selectively to target a single well-defined process; and normal prescribing practice for infections in the community seems to be to use one antibiotic at a time. So, if the solution to the antibiotic resistance problem is not to be found in "out of the box" targeting of, for example, quorum sensing processes or plasmid-mediated processes, should we not instead be contemplating how to mix and match a cocktail of antibiotics to simultaneously target several processes for each particular infective organism? We do this for Helicobacter pylori infections (but treatment failure can still be an issue when the particular strain in a given patient is already resistant to one of the antibiotics in the cocktail). But this approach still ignores the effects of those antibiotics on the patient's microbiome: in clearing the infection, the collateral damage inflicted on the patient's microbiome by the antibiotic cocktail is likely to lead to iatrogenic disease ... which is, of course, considered to be an acceptable price to pay by those undergoing life-saving cancer chemotherapy. But such a strategy could also increase the risk of antibiotic resistance emerging in normally commensal skin, nasopharyngeal, vaginal, gut, etc. bacteria.

    If was forced to bet on the matter, my money would be on the microbes always being one step ahead of humans simply because they are able to evolve their avoidance strategies faster than we can discover and develop (or evolve) new antibiotic strategies. Indeed NESTA acknowledges this explicitly: "We cannot outpace microbial evolution. A new broad-spectrum antibiotic, if applied with current methods, would eventually meet new forms of resistance."

    The problem is not that there are no new antibiotics to be found but that the pharmaceutical industry finds it difficult to make a business case to develop new antibiotics. This is because each super new antibiotic is deliberately (and for obvious reasons) put in a cupboard marked "Do not use except as an absolute last resort". The pharmaceutical industry needs antibiotics to be used in significant quantities in order to generate an income stream. Perhaps what we really need is for organisations such as NESTA and for governments to put money into a global not-for-profit endeavour that develops, perhaps under the auspices of WHO, new antibiotics to put into those locked cupboards, to be used only when all else has failed.


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