Antimicrobial Resistance: Can We Outrun Evolution?

First published in the NASGP Newsletter in February, 2020

This was written at the end of January 2020. Since then Covid-19 has trumped almost every other medical challenge, but in the future we will need effective antibiotics all the more.

In his Nobel prize acceptance speech Alexander Fleming sounded a note of warning. He had seen microbes acquiring resistance to penicillin and foresaw that misuse of the drug could undermine its effectiveness.

Recently, at the Frontline Club across the road from Fleming’s old lab, five people whose work as journalists and doctors has helped to bring that threat to public attention reviewed the current crisis. They included former Chief Medical Officer for England Dame Sally Davies and Times journalist David Aaronovitch – whose life was saved by antibiotics when he developed sepsis after a routine operation went wrong. They all expressed the hope that, with a bit more pushing, antimicrobial resistance (AMR) will have its David Attenborough moment.

Not at Davos; Health Secretary Matt Hancock’s speech at the meeting of the world’s movers and shakers was anodyne. And coronoavirus has wiped other health threats from the headlines.

In the pre-antibiotic era – only 75 years ago – a tiny scratch could lead to sepsis and a 95% chance of death. In 2020, most trivial injuries need only simple antibiotics or none but, if you are unlucky, a multi-resistant organism can kill you. The economic consequences of AMR are already alarming. It costs the NHS around £100 million each year. The estimates for 2050 are US$100 trillion and 10 million deaths worldwide.

Unless things change, over the next 30 years modern medicine will be undermined. If there were no antibiotics would you consent to a joint replacement or abdominal surgery? Would you accept chemotherapy? Would you let your kids go on an adventure holiday?

If no-one is buying their money-spinning cancer treatments, drug companies might risk the investment to develop antimicrobials.

Those who spoke at the Frontline Club hope it isn’t too late. They hope we can develop new antimicrobials, reduce overuse and misuse to preserve the effectiveness of those we already have, and reduce the need for antimicrobial treatments.

Because Big Pharma puts profits ahead of its social obligations, it’s 30 years since we last saw a new antimicrobial. Yet, if companies discover that no-one is buying their money-spinning cancer treatments because immunocompromised patients are dying from resistant infections they might decide to risk the investment to develop antimicrobials. Phages offer a new approach. Because that investment is huge, distasteful though it may be to give Big Pharma tax-payers’ money, partnership between governments, the pharmaceutical industry and charities is probably essential.

Meanwhile, we have to regard antimicrobials as a non-renewable resource and husband those we have. Antimicrobial stewardship is a mechanism through which everyone involved with antibiotics promotes good prescribing practice and monitors the results. It’s worked in hospitals to reduce MRSA and C diff infections. Hopefully the remit of stewardship includes being honest: not suppressing press releases and not discouraging the acknowledgement of AMR on death certificates.

There’s been some progress. British GPs are now writing fewer prescriptions for antimicrobials. There are always some patients whose demands can be hard to manage, but most people don’t expect antibiotics the way they did 20 years ago. And strep throats still respond to penicillin.

It isn’t just doctors who prescribe antibiotics. So, one must hope that paramedics and others are also stewarding their prescribing. But in much of the poor world people still die for want of an antibiotic. Where there are no proper medical services there is no-one to turn to except quacks. How can the quacks be regulated?

So far, so fairly good, but far more antibiotics are prescribed to cows than to humans. Not because animals are sick; it’s to fatten them up. So, it’s not surprising that it’s in agriculture that a lot of the resistance develops. Use as growth stimulants in UK is falling. Even in Bangladesh, where antimicrobial security has to be weighed against food security, educating farmers and vets and restricting sales have dented the use of antibiotics.

Resistance also breeds in the antimicrobial-laden effluent we pump into our environment. Regulation and monitoring of discharges from pharmaceutical production plants is realistic, but unfortunately there is as yet no way of removing most medications from sewage. And we can’t stop AMR spreading in the droppings of migrating birds.

Prevention is better than cure. We can – we have to – reduce the need for antimicrobials. Fewer germs equals fewer infections. Epidemics arise in crowded environments, and so does AMR. Provision of decent water supplies and sanitation, better housing and adequate food may be out of a GP’s control, and we can do little to bring political stability and reduce conflict, but we can all wash our hands properly. Hospital campaigns do work – for a while, but even those who should know better become lax. In a toilet at my local hospital were four tatty notices about hand washing. One bold poster, replaced regularly with a new one, would demonstrate that the hospital takes handwashing seriously.

Public education is the key. Some patients firmly believe that it is they, not the ‘bugs’, that have developed resistance to antibiotics. But AMR is now on the curriculum, and the young, who have their future to lose, should have a better understanding. I saw a sell-out musical at the Edinburgh Fringe in 2018, The Mould that Changed the World. It has spun off professional and school productions that are bringing the word about bacterial resistance to children and their parents.

Young adults too need information in a form they relate to. Media and formats designed by millennials for millennials may make older people cringe, but they will be more effective for their target audience than tasteful leaflets. And we shouldn’t be afraid to shock: HIV ads in the 1980s worked. And how about a Love Island contestant with resistant GC?

Then there’s immunisation: modern medicine’s biggest achievement at reducing infections. Medics and journalists must refute the misinformation spread by antivaxxers while new vaccines are developed.

Is this another war which we can never win? Can we outrun evolution? It’s a much more difficult problem than tobacco control. WHO has been issuing regular resolutions on AMR since 1998. In 2011 CMO Dame Sally Davies drew attention to the dangers, and – eventually, in 2014 – PM David Cameron announced a review and called for global action. In 2019 the Secretary General of the UN endorsed it. Yes, actions have been taken, here, there and around the world, but despite worthy promises there has been no One Health approach – governments, civil societies and industrial organisations co-operating. Can Dame Sally’s current work on the UN Inter-Agency Coordination Group on AMR tip words into actions?

Having no antimicrobials wouldn’t be the end of life on earth – humans existed for thousands of years without them – but it would be the end of life as we have got used to living it. Going back to the fears and tragic early deaths of the pre-antibiotic era is – let us hope – an avoidable disaster.

Postscript: Shortly after this article was written in late January 2020, it was announced that machine learning had generated a totally new antibiotic.