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antibiotic

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Oh dear, we’re all going to die from resistant bacteria and it’s all the doctor’s fault … again!

At least, that’s the message from the recent newspaper headlines. Apparently, overprescribing GPs will be struck off, or at least disciplined by the GMC. However, the media brouhaha, as usual, obscures the real picture.

If you believe the press reports, every patient in the UK with a sore throat is automatically provided with bucket-loads of the newest antibiotics by malicious GPs. But before we start listening to the media’s calls to discipline these ‘offending’ GPs, we should look at the wider picture.

The media coverage was sparked by the publication in August of the NICE guidance on ‘antimicrobial stewardship’. Professor Mark Baker, director of the NICE Centre for Clinical Practice is on record as saying that antibiotics must be used ‘more sensibly’ and suggesting that GPs who prescribe too many antibiotics should face sanctions [1].

There is no doubt that GPs are under considerable pressure to prescribe antibiotics. A survey commissioned by Nesta in 2014 found that 90% of GPs say they feel pressure from patients to prescribe antibiotics and 70% say they prescribe because they are unsure whether the infection is bacterial or viral [2]. Other research reinforces the impact of patient pressure: 44% of GPs have admitted to prescribing antibiotics just to get a patient to leave the surgery [3].

So two things are going to help GPs to meet the recommendations in the NICE document:

  • Accurate point-of-care diagnostic tools
  • Help with communication skills and strategies to help educate patients

Improved point-of-care diagnostics can help the physician to be sure that the patient’s symptoms are caused by bacteria that will respond to antimicrobials. There are some diagnostic tools already available in some countries but these tend to be time consuming and not terribly accurate. The Nesta Longitude Prize 2014 has set a challenge to create cost-effective, accurate, rapid and easy-to-use tests for bacterial infections that will help health professionals worldwide [4]. The prize fund is £10m and entries for the prize are already being submitted – the final closing date is 2019 but the first entry to successfully meet the criteria will win the prize.

Feedback and education

There have already been several programmes that have proved successful in reducing overprescribing and provided insight into the factors that influence primary care physicians in their prescribing. For example, in 1995 the Swedish Strategic Programme against Antibiotic Resistance (STRAMA) was launched and demonstrated the importance of providing information feedback to GPs and allowing them to reflect on their own prescribing. The guiding principle underlying STRAMA was to provide prescribers with feedback on local prescribing or resistance patterns so that they can compare their own prescribing with anonymised data for their colleagues. The programme brought about a steady reduction in antibiotic use in Sweden between the mid1990s and 2004 [5].

The NICE guidance also acknowledges the importance of patient education to the success of antimicrobial stewardship but doesn’t suggest how this can be achieved. Physicians constantly face patients who ‘know that antibiotics is what I need, Doctor’ and the 8-10 minute typical consultation can easily lead to defensiveness and frustration. Media campaigns to educate patients about antibiotics are typically unsuccessful but there are model interventions that have been shown to work. For example, a recent study in Wales shows that actively supporting the GP with up-to-date education and enhanced communication skills can help to make the consultation itself a successful patient education initiative. The STAR programme (Stemming the Tide of Antimicrobial Resistance) achieved a 4.2% reduction in total oral antibiotic prescribing in 34 practices in Wales without significant changes in admissions to hospital, reconsultations or costs. The programme comprised five sessions of web-based training and an expert-led, face-to-face seminar [6]. The online training included case-based scenarios, provision of up-to-date research evidence and guidelines, and training in the communication skills to help educate the patient without conflict. Participants were happy with the programme and reported an increased awareness of the issues of antibiotic resistance and increased insight into the patient expectations, which in turn improved the consultation [7].

Not the whole story

However, even if the NICE guidance does have the desired effect, there is still an elephant in the room: resistance resulting from animal and environmental antibiotics.

Across Europe and the US, at least as much tonnage of antibiotics is used in agriculture as is used in human medicine. Although there is still dispute, there is a considerable weight of evidence that agricultural antibiotic use is the main source of resistance in Salmonella and Campylobacter infections and contributes significantly to E.coli and entrococci infection [8].

There are many routes for antibiotic resistance to be transferred from sources outside the healthcare system:

  • Direct contact: farm and slaughterhouse workers can be infected by resistant bacteria [9 and references therein] enabling transmission to the community
  • Through the food chain: this is challenging to prove but the weight of evidence is accumulating with an increasing number of reports in the literature
  • Through exposure to bacteria in the environment: in addition to hospital waste, 75-90% of antibiotics used in food animals are excreted unmetabolised into the environment [9]

Actions taken so far include the banning of non-therapeutic use of antibiotics in farming (although some countries still permit the use of antibiotics as growth enhancers)

The WHO has established a list of antimicrobial agents essential for human health – agents that should not be used for treating animals. However, compliance with the WHO regulations is neither mandatory nor regulated [10]!

The environmental risks should be mitigated by improving industrial systems for sanitation and decontamination of hospital sewage water.

So although GPs undoubtedly carry a responsibility for the careful prescription of antibiotics within the healthcare system, the things they aren’t responsible for include:

  • Implementation of linked AMR surveillance systems that will provide accurate monitoring and reporting of resistance
  • Educating farm workers and everybody involved in ‘farm-to-fork’ food chain
  • Policing which antibiotics can be used for treating animals, avoiding all those that have been identified as essential for human health
  • Developing strategies for reducing the risks of environmental exposure
  • Discovering new antibiotics – the pipeline is currently empty!

I guess that once governments and global agreements have solved all these issues, not just alleged overprescribing, it will be OK to consider striking off GPs. But not until then!

 

If you would like to comment on any of the issues raised by this article, particularly from your own experience or insight, Healthcare-Arena would welcome your views.

References

  1. GPOnline (2015): http://www.gponline.com/gps-face-sanctions-inappropriate-antibiotic-prescribing-says-nice/article/1360344. Accessed August 2015
  2. Nesta, Antibiotic prescribing survey (2014): http://www.nesta.org.uk/news/%E2%80%98benefit-doubt%E2%80%99-basis-prescribing-antibiotics-finds-longitude-survey. Accessed August 2015
  3. Cole A. GPs feel pressurised to prescribe unnecessary antibiotics, survey finds. BMJ. 2014;349:g5238.
  4. Nesta Longitude Prize (2014). http://www.nesta.org.uk/news/ps10m-longitude-prize-opens-today-tackle-antibiotic-resistance. Accessed August 2015
  5. Molstad S, Cars O, Struwe J. Strama–a Swedish working model for containment of antibiotic resistance. Euro Surveill. 2008 Nov 13;13(46).
  6. Butler CC, Simpson SA, Dunstan F, Rollnick S, Cohen D, Gillespie D, et al. Effectiveness of multifaceted educational programme to reduce antibiotic dispensing in primary care: practice based randomised controlled trial. BMJ. 2012 Feb 2;344:d8173.
  7. Bekkers M-J, Simpson SA, Dunstan F, Hood K, Hare M, Evans J, et al. Enhancing the quality of antibiotic prescribing in Primary Care: Qualitative evaluation of a blended learning intervention. BMC Fam Pract. 2010 May 7;11:34.
  8. ASOS (Alliance to Save Our Antibiotics (2015) ‘Antimicrobial resistance – why the irresponsible use of antibiotics in agriculture must stop’: http://www.ciwf.org.uk/media/7247793/antibiotics-alliance-40pp-report-2015.pdf. Accessed August 2015
  9. Marshall BM, Levy SB. Food Animals and Antimicrobials: Impacts on Human Health. Clin Microbiol Rev. 2011 Jan 10;24(4):718–33.
  10. WHO (2012): Critically important antimicrobials for human medicine. http://www.who.int/foodsafety/publications/antimicrobials-third/en/. Accessed August 2015.

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Microbiome data now being gathered may form the basis for a ‘personalised’ approach to improving individual microbial populations

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In May 2015, a molecular microbiology study was published in the Proceedings of the National Academy of Sciences (1). This study showed that gut bacteria could be DNA ‘fingerprinted,’ as their DNA sequences were shown to represent a unique form of identification in more than 80% of individuals examined (1). This study has little to do with ‘CSI’-style forensic identification but does have implications for our health, diet, development and genetics and our ability to defend ourselves from true microbial pathogens (1).

That the human body is believed to contain ten times more microbial cells than human cells (trillions of them) can be an uncomfortable thought. Even more remarkable is that, in terms of numbers, the population of these microbes accounts for up to 90% of the total number of cells associated with our bodies. Our human microbial population weighs between 1% and 3% of our total body mass (1.5 kg); this is equivalent to the weight of the largest human internal organ, the liver (2).

The terminology of the body’s flora and fauna can be confusing. This could be why someone, probably working in advertising, came up with the phrase ‘friendly bacteria.’ The term ‘microbiota’ is the collective noun that refers to the viruses, fungi and bacteria that inhabit our bodies, mainly in our gut and on the surface of our skin. The microbiota has a commensal and a symbiotic relationship with us. The term, ‘microbiome’ is used to refer to the collection of the genomes of these microbes. These two names, ‘microbiota’ and ‘microbiome,’ are often used interchangeably.

Our view of our personal microbial health has changed during the past 20 years. Until the 1990’s there was the ‘germicidal view’ that all bacteria were harmful and that we should be doing all we could to sterilise our home environment, ourselves and our food. There are now increasing numbers of scientific and healthcare news stories, as well as television commercials, which advise us to encourage and nurture our own, resident, and very personal ‘friendly bacteria.’

As with the dietary anti-oxidant ‘industry’ that arose from cardiovascular research in the 1980’s, the food industry has been swift to promote the sales of dietary probiotic supplements. Global sales of probiotics have been reported as £13.6 billion ($21.6 billion USD) in 2010 and are expected to exceed £19.6 billion ($31.1 billion USD) during 2015 (3).

In February 2015, an editorial collaboration between the journals, Nature and Scientific American, resulted in the publication of a series of special reports entitled, Innovations in the Microbiome(4) These and other recent publications have helped to place the importance of the normal human microbial population further into the medical spotlight.

For almost a century, epidemiological studies have shown that diet has a profound effect on human health. Recently, the link has been made between diet and the gut microbiota, with emphasis on the effects that a ‘western’ diet of refined foods and high protein have on these organisms. In 2011, a study linked long-term dietary patterns to changing gut bacterial enterotypes in humans (5). In 2014, a study in wild mice clearly demonstrated that dietary change can induce gut bacterial ‘enterotype switches’ within hosts (6). ‘Biome reconstitution’ has been proposed as a treatment approach to immune disorders, including allergy and autoimmune disease and to preventing colonic cancer, obesity, diabetes, and metabolic disease (7, 8).

In the past ten years, sequencing technologies have allowed the development of a detailed reference database of the diverse microbes that inhabit our bodies. In 2007, in the US, the National Institutes of Health (NIH) Human Microbiome Project (HMP) Consortium was launched, consisting of more than 200 members, from nearly 80 universities and scientific institutions (9). In its 2012 report, the HMP listed the major ways in which knowledge of the human microbiome may change the future of science and medicine (10). The HMP has considered the potential privacy issues surrounding knowledge of the individual microbiome, the flow between human microbes and those found in nature (in water and soil) (10).

The microbiome data now being gathered may form the basis for a ‘personalised’ approach to improving individual microbial populations. Most importantly, solutions to microbial antibiotic resistance may be found through increasing knowledge of microbial interactions. At this same time comes the realisation that overuse of antibiotics, as part of our ‘war on germs’ mentality, has allowed true microbial pathogens to develop antibiotic resistance. The lack of a functioning and complete personal microbial population leaves us vulnerable to bacterial pathogens that we may be increasingly less able to fight.

In 2013, the Chief Medical Officer for England highlighted the increasing problem of antibiotic resistance. These concerns led to the Department of Health launching a five-year Antimicrobial Resistance (AMR) Strategy, which is supported by NHS England’s Antibiotic Awareness Campaign (11,12). In October 2014, Public Health England produced the first report on the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) (13). These latest initiatives by the medical profession and healthcare regulators to reduce antibiotic prescribing is just one approach that has to be made.

The European Molecular Biology Laboratory (EMBL) annual conference, held in Heidelberg in June 2015, was devoted to the topic of the Human Microbiome (14). This meeting included discussions on the design of possible therapeutic or dietary interventions to prevent and treat disease. An announcement was made at the meeting of the first results from the Personalised Nutrition Project, run by research groups in Israel (15). The u-Biome Project is a crowdfunded ‘citizen science’ initiative that is set to analyse the microbiome in the context of individual health and is currently recruiting participants (16).

The rationale for learning more about the ‘normal’ or ‘optimal’ microbiome, and how to reconstitute or nurture it, is an important component of individual healthcare (17, 18). For the future development of interventions for resistant microbial pathogens, the human microbiota may play more than just a ‘friendly’ role, it may be life-saving.

If you would like to comment on any of the issues raised by this article, particularly from your own experience or insight, Healthcare-Arena would welcome your views.

References

(1) Franzosa EA, Huang K, Meadow JF, Gevers D, Lemon KP, Bohannan BJ, Huttenhower C. Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci U S A. 2015;pii 201423854. http://www.pnas.org/content/early/2015/05/08/1423854112 Accessed June 10, 2015

(2) The Human Microbiome Project. Structure, function and diversity of the healthy human microbiome. Nature 2011;486:207-14. http://www.nature.com/nature/journal/v486/n7402/full/nature11234.html Accessed June 10, 2015

(3) Business Communications Company (BCC) market research data for sales of probiotic foods and supplements, 2010 and 2015. http://www.bccresearch.com/pressroom/fod/global-market-for-probiotics-reach-$36.7-billion-2018 Accessed June 10, 2015

(4) Special Report. Innovations in the Microbioma. Scientific American Vol 312, Feb 2015. http://www.scientificamerican.com/editorial/innovations-in-the-microbiome/ Accessed June 10, 2015

(5) Wu GD, Chen J, Hoffmann C, et al. Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes. Science 2011;334(6052):105-108. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368382/ Accessed June 10, 2015

(6) Wang J, Linnenbrink M, Kunzel S, et al. Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice. Proc Natl Acad Sci USA 2014; 111:E2703-E2710. http://www.pnas.org/content/111/26/E2703.full Accessed June 10, 2015

(7) Parker W, Ollerton J. Evolutionary biology and anthropology suggest biome reconstitution as a necessary approach toward dealing with immune disorders. Evolution, Medicine, and Public Health 2013;2013(1):89-103. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868394/ Accessed June 10, 2015

(8) Grice EA, Segre JA. The Human Microbiome: Our Second Genome. Annual Review of Genomics and Human Genetics 2012;13:151-170. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518434/ Accessed June 10, 2015

(9) The National Instututes of Health (NIH) Human Microbiome Project website http://commonfund.nih.gov/hmp/index Accessed June 10, 2015

(10) National Institutes for Health (NIH). Human Microbiome Project defines normal bacterial makeup of the body. Genome sequencing creates first reference data for microbes living with healthy adults. June 13th 2012. http://www.nih.gov/news/health/jun2012/nhgri-13.htm Accessed June 10, 2015

(11) The Department of Health Antimicrobial Resistance (AMR) Strategy 2013 to 2018. First published September 10, 2013. https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018 Accessed June 10, 2015

(12) NHS Antibiotic Awareness Campaign. Last revised 24th Sept 2014. http://www.nhs.uk/NHSEngland/ARC/Pages/AboutARC.aspx Accessed June 10, 2015

(13) Public Health England. English Surveillance Programme Antimicrobial Utilisation and Resistance (ESPAUR) Report. Published Oct 10, 2014. https://www.gov.uk/government/publications/english-surveillance-programme-antimicrobial-utilisation-and-resistance-espaur-report Accessed June 10, 2015

(14) European Molecular Biology Laboratory (EMBL) website. http://www.embl.de/aboutus/general_information/index.html Accessed June 10, 2015

(15) The Personalised Nutrition Project website. http://newsite.personalnutrition.org/WebSite/Home.aspx Accessed June 10, 2015

(16) u-Biome – Sequencing Your Microbiome website. https://www.indiegogo.com/projects/ubiome-sequencing-your-microbiome#/story Accessed June 10, 2015

(17) Grogan D. Microbes in the Gut Are Essential to Our Well-Being. Scientific American. Feb 17, 2015. http://www.scientificamerican.com/article/microbes-in-the-gut-are-essential-to-our-well-being/ Accessed June 10, 2015

(18) Parums D. ‘Indigenous’ Human Microbes – the Microbiota and the Microbiome. Thomson Reuters Life Sciences Connect. May 26, 2015. http://lsconnect.thomsonreuters.com/indigenous-human-microbes-the-microbiota-and-the-microbiome/ Accessed July 6, 2015

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