6 important lessons to learn about antibiotic resistance – AMR Event 2016

On 17th November, in collaboration with the University of Manchester’s Division of Population Health, Health Services Research & Primary Care and ReThinkX, we held an open event on antibiotic resistance at CityLabs, in Manchester. We invited exemplary professionals working on different facets of a global problem. The event was largely attended by interested university students; however, its insights resonate far beyond the confines of one lecture theatre on one evening. 

What lessons could be derived from a general practitioner, a Professor of Economics, research nurses, a historian, and a public health consultant?

If you missed our first post, which provides a basic overview of the problem, see here.

1. Fund interventions at a primary care level

Professor Aneez Esmail’s opening remarks as Chair of the event:

People are getting infections all the time; we’re aware of how common they are

Speaking from his direct and extensive clinical experience as general practitioner (G.P.), he reported that G.P.s were beginning to access diagnostic tools designed to support the rational prescribing of antibiotics. In the United Kingdom, 87% of prescriptions for antibiotics for the human population occur within primary care.

Professor Esmail is currently Director of the NIHR’s Manchester Patients’ Safety Translation Research Centre. He incisively observes how funding streams for research can misdirect our solutions to a given problem. As a powerful example, he described that it was the application of a sociological rather than  a traditionally biological lens – which observed that parents of Asian families laid their babies on their back, and tended to have them sleep in the same bedroom – that led to the most impactful reduction in the incidence of cot-deaths (or ‘sudden infant death syndrome’, SIDS). The molecular, microscopic, explanations being contemporaneously investigated had missed this perspective. In the case of antibiotic resistance, where funding streams are biased towards a drug development agenda, we may be at risk of becoming reductionist in our strategy.

The answers don’t come from one group of people… it was eye-opening to see [from historian Dr Claas Kirchhelle] that this is not a new problem

2. Antibiotics should be perceived, protected, and treated as a shared global resource

We spoke to Professor Ramanan Laxminarayan, an authority on the subject at the Centre for Disease Dynamics, Economics and Policy at Princeton University, over a thready Skype connection whilst he was Johannesburg.

He highlighted that antibiotics are a shared resource, just like our climate.

He extended this analogy – the problem is a consequence of many people playing  a role in the problem, with small numbers of actors. And that we are drawn to the belief that, owing to the scale of the problem, our individual contributions cannot be significant.

He highlighted that whilst mechanisms of antibiotic resistance were evident prior to their clinical use in 1949, we never previously considered that they could evolve into a serious public health threat. Warning signs are surfacing: resistance previously only observed in the hospital setting are being observed in the community, and we are beginning to see patients with infections which cannot be treated by any antibiotic. In some Indian hospitals, carbepenem resistance has been documented as high as 70% or 80%.

Unfortunately, resistance is an irreversible phenomenon. In the bacterial population, the prevalence of bacteria carrying ‘resistance genes’ to specific antibiotics is rare, set at approximately 1 in 1,000,000. However, continued and indiscriminate use of antibiotics selects out non-resistant bacteria, leading to a noticeable increase in the population prevalence of resistant bacteria. Resistance traits are passed or ‘translocated’ between bacteria of different strains, to the point where the characteristic becomes noticeable and prevalent – 1 in 100, then 1 in 10, then 1 in 2. At this level of prevalence, it is impossible to reverse resistance to a particular antibiotic, effectively rendering the medication useless.

He concluded his thoughts with some criticisms – specific goals rather than aspirations need to be set out by the WHO, with funding channeled into new diagnostics and vaccines that might preclude the use of antibiotics altogether.

View Dr. Enrique Cástro-Sanchez’s slides here

3. Antimicrobial resistance is a social, cultural and economic problem

Dr. Enrique Castro-Sánchez, a Research Nurse who works under a collaboration between the Wellcome Trust and Imperial College, scrutinises the role played by human factors and fallibility. Antibiotic prescribing is a behavioural phenomenon rather than a perfect, linear, process, and not all those who handle antibiotics do so appropriately and cautiously. Interventions to raise awareness carry limited durability as interest in the issue decays with time – after all, the subject can Antibiotic use decreases with public engagement, which cycles.hardly be considered glamorous.

‘The use of information, and ‘gossiping’ – forming ‘mindlines’ rather than ‘guidelines’ – could explain the failures of policies

From the side of the public, there is a mixed level of understanding. He discussed how it was often a matter of cultural perception and expectation – for instance, in his home country, in Spain, the average person might not be able to see a G.P., and therefore, the incentive might be to:

pop along to the pharmacy and self-diagnose

In the United Kingdom, operating under a culture of 10 minutes per patient, antibiotics can be perceived as a means of ‘diplomacy’ between doctor and patient – prescribed to placate a patient who perhaps doesn’t understand the nuances of antibiotic use. He highlighted that hotspots of antibiotic prescription co-localised to deprived areas. Much of the problem – both in prescribing to humans and their unreserved use in animals – may be rooted in education and literacy.

Drugs and bugs are so last season… if we’re not looking at the determinants, we might as well give up and go to the pub.

View Dr. Claas Kirchhelle’s slides here

4. Historical analysis can point to blind spots that have prevented previous regulation from being effective

Dr. Claas Kirchhelle – a historian based at an interdisciplinary group at Oxford – took us on a fascinating journey, distilling the key moments of the antibiotic saga. This began with the pre-penicillin era, during which antibiotic prescribing had already begun with the Sulpha drugs.

The pipeline is emptyingThe 1940s and 1950s saw the gold-rush of discovery of new antimicrobial compounds. Pfizer, a large pharmaceutical company, began to advertise antibiotics to farmers, complementing the ‘Wave of Gluttony’ of the 1950s that saw farmers under great pressure to upscale their food production. Farming was no longer considered to be a ‘dirty’ industry, but rather, scientific and predictable; antibiotics were used to promote the growth of poultry and cattle. Other uses included plant protection, food preservation (poultry carcasses, fish fleets), and to my surprise, even in whale harpoons (the antibiotic was released into the dying animal’s circulatory system, helping to prevent degradation). To this day, the majority of antibiotic use occurs within the agricultural sector, which has arguably been the main driver of resistance.

Agriculture accounts for the greatest use of antibiotics.

Agriculture accounts for the greatest use of antibiotics.

Antibiotics were used excessively in the post-war period; a great deal of optimism was invested in the industry’s ability to ‘stay ahead’ of resistance. Indeed, the contemporary understanding of resistance was different; it was believed that resistance could only be vertically transmitted (from one generation of bacteria to the next). In the 1960s, Japanese research overturned this belief, demonstrating that the horizontal transfer (between bacteria) of traits was possible. This led to the development of early containment strategies, which consisted of public education, rational drug use, infection control, and antibiotic restriction (licensing only if efficacious).

He emphasised that it would be overly simplistic to blame the ‘ignorant public’ and ‘greedy farmers’. The pharmaceutical industry should also be held accountable, as are professionals, who have a duty to function as ‘gatekeepers’.

In the modern era of antibiotic use, new mechanisms have come into play – antibiotic innovation and enhanced surveillance.

View Dr. Will Welfare’s slides here

5. For policymakers, stories and numbers are vital

As a consultant in Health Protection for Public Health England, Dr. William Welfare splits his time between reacting to outbreaks of infectious organisms, and addressing the problem at its source.

There are questions that precede his decision-making –

Why should I care? Why is this important?

In the information era, Public Health England can presently track what people Google, what people complain of across social media outlets, who’s phoning NHS 111, G.P. visits (through read-codes entered by G.P.s), who’s visiting the out-of-hours, and are notified about A&E presentations and hospital admissions. They track bugs and track drugs. This provides ample material for the surveillance of antibiotic use and resistance. The nature of resistance is that if it affects one hospital, it affects many.

I want to change what appears on Aneez’s computer to make it easy for him to prescribe the right thing

The line struck me as the most direct and easily visualisable connection of the evening.

The team is currently engaging in active case searching for carbapenemase-producing Enterobactericaea through the tracking of the presence of specific genetic elements.

He prompted us to consider that only a small minority of the bacterial population could be sampled by public health, as the large majority of infections go un-sampled and uncultured and moreover, many of us are healthy carriers of bacteria, without developing infection.

None of it matters until people get ill with it –  only a minority of patients will give their G.P. a sample, which undergoes bug detection and sensitivity testing; therefore, information is based on a small minority of people

You all are brilliant vectors for antimicrobial resistance… you probably won’t let me do surveillance on you… so we’re tracking what’s going in the sewage plants

Public health teams, by bringing together laboratory, health service, and animal, data, are operating at the frontline of the problem.

View Dr. Katie Reed’s slides here

6. We can draw valuable comparisons between antimicrobial resistance and major epidemics, such as malaria

Dr. Katie Reed, a nurse and midwife of an extensive background of international field experience, drew valid comparisons between antibiotic resistance and the malaria epidemic. Resistance is no foreigner to medicine. Populations have developed resistance to antimalarial medications, which forms the rationale for ‘combination therapy’ – the use of multiple drugs to circumvent resistance to 1 or 2 drugs – a strategy also developed for tuberculosis regimens (‘multi-drug resistance tuberculosis’ or MDR-TB).

The use of such medications vary between groups. However, for malaria, the development of resistance disproportionately impacts women and children aged less than 5 years; therefore, individuals are responsible for carrying and spreading resistance to vulnerable groups.

Reiterating points rise by Enrique Castro-Sanchez, people do not use antibiotics in the same manner. In Pailin, Cambodia, 70% of Cambodians buy their medications from the private sector. For illegal migrants unable to access public facilities, treatments are bought privately. For the average man, the priority is to remain productive and continue to work.

Dr. Reed emphasised the essential need for rapid diagnostic testing to prevent inappropriate use, as well as the implementation of social marketing projects, voucher schemes, and the support and education of private sector outlets who have a vested interest in selling medications, even if unnecessary.

Post-hoc reflections

As a nonspecialist, the event was replete with insights and connections I hadn’t previously considered, and confirmed those I had – in my second year, I undertook a week-long placement during which I spent time in a microbiology laboratory of a large Scottish hospital and first-handedly observed sensitivity and susceptibility testing take place on patient samples.  Once again, the event reinstated how professionals outside of clinical medicine are often best placed to undertake a holistic and critical analysis, providing a non-clinical perspective for an issue very much intertwined with clinical medicine and the future of these essential medicines.

Anahita Sharma is a 4th-year medical student, and currently Editor for the MCR Global Health Society.

One Response to “6 important lessons to learn about antibiotic resistance – AMR Event 2016

  • Roger Harrison
    10 months ago

    Hi – this is an excellent account of the evening seminar, and a strong reminder of the global impact antibiotic resistance is having. When organising this event with the Global Health Society, my aim was to bring together professionals from a range of different disciplines, but all interrelated to the wider determinants of health. The talks they gave clearly showed the relevance of thinking about all vectors that impact on health, now and in the future.

    There isn’t a single solution to prevent AMR worldwide, nor is AMR actually preventable. What we have to do, and the ‘have’ is a must, is to ensure all existing, effective strategies are used to the maximum level possible, and that new investigations are carried out to obtain evidence of their likely benefit. The topic also highlights a need to continually expand on wider aspects associated with health in general – and the strongest influence of this is without doubt poverty and social inequalities.

    Well done to the GHS and their colleagues for running the successful event and I hope it now acts as a catalyst for future work on this subject.

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