Clinicians and antibiotic resistance: What does the future hold?

If global health experts’ warnings of a new “post-antibiotic” medieval era for public health have not made you sit up and take notice, perhaps a recent focus by the notoriously penny-wise pensions industry will do the trick.

And while the press headlines may be hysterical in their reporting of this public health threat, the latest edition of Institute and Faculty of Actuaries magazine Longevity Bulletin was sobering.

Authors highlight fears that deaths from antimicrobial resistance will rise from around 700,000 annually now to 10 million a year by 2050 to become the number one cause of death. This avalanche of fatalities would see global GDP fall 2-3.5 per cent, costing the world up to £66 trillion, it is suggested.

But it is a contribution by a senior consultant with risk management firm Willis Towers Watson that serves up one of the most striking observations.

Their attempt to calculate the likely impact of antimicrobial resistance concludes that, while a return to the pre-antibiotic era is “unlikely,” “it is evident that the mortality increases from antibiotic resistance could match or even outweigh longevity improvements.”

In effect, the message is that projected rising life expectancy through better health and care could slow dramatically or be stopped in its tracks.

Antimicrobial resistance is certainly not a new phenomenon, being first identified in the 1940s with penicillin.

What is new is the rapid evolution of resistant strains through novel defence mechanisms that prevent or repel the entry of antibiotics into a bacterium, as well as rising incidences of resistant infections in general.

The contributory causes are well documented. Prescription of antibiotics by GPs was long almost a given among those presenting with relatively minor symptoms – General Practice accounts for 80 per cent of UK antibiotics prescriptions, and around half of that figure are simply for chest infections.

But a 2014 World Health Organisation report into the phenomenon has since prompted policy-makers to act. Its authors warned: “Without urgent, coordinated action, the world is heading towards a post-antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill.”

Last year saw a 7.3 per cent reduction in antibiotics prescribed by England’s GPs, down around 2.6 million to 34m. It has not been a cost-free exercise – the government has opted to pay Clinical Commissioning Groups a reward if their reduction targets are hit. Many CCGs, in turn, have offered cash incentives of up to £20,000 to GPs to cut the numbers.

Yet the response was branded “a fantastic result” by NHS Improvement’s Dr Mike Durkin.

When it comes to hospitals, which account for the other 20 per cent and naturally generally the more acute cases, the situation is more complex.

Part of the problem lies in the speed at which an accurate diagnosis can be made prior to treating a patient.

In cases where a patient may be infected by a resistant organism, the impact of “initial inadequate antibiotic treatment” (IIAT) – ineffective broad spectrum treatment received by a patient prior to identification of the specific organism in question – can prove deadly.

Dr Meghan Perry and Professor Mark Woolhouse of the University of Edinburgh’s Epidemiology Research Group highlight the links between IIAT and longer hospital stays, as well as a three-fold increase in the risk of death.

And by increasing the time it takes to treat a resistant strain the risk of transmission to and then by staff and other patients is all the greater.

In hospitals part of the solution lies in enacting and policing well-known mantras – to only prescribe and dispense drugs when they are needed, to enhance and police infection prevention and control, and to dispense or prescribe only the correct type of antibiotic for the illness in question.

But also important both in hospitals and surgeries is rapid diagnosis – something that remains elusive.

Indeed that’s the thinking behind the £10 million Longitude Prize, a project established in 2014 to encourage the development of a cheap, accurate, rapid and easy-to-use point of care test kit for bacterial infections.

“Clinicians often prescribe broad spectrum antibiotics to sick patients because doctors have to act quickly on imperfect information,” say the organisers. “These methods put selective pressure on microbes to evolve resistance to antibiotics.

“The overall solution involves a long-term path towards a more intelligent use of antibiotics enabling a future of more effective prevention, targeted treatments and smart clinical decision support systems.”

But if diagnosis and prevention are part of the solution, what of the cure?

Following a 30-year hiatus in their development, the race to produce the latest antibiotic “bunker buster” in this arms race is proving slow going.

Nevertheless, around 39 new antibiotics are currently in clinical development, including two representing new classes.

One of these is designed to target gram-positive bacteria and works by binding to fatty molecules to impede the production of cell walls, causing the cells to break down. It is still awaiting human trials.

Another is a “defensin-mimetic,” so called because it is modelled on the natural human immune proteins. It is currently at stage two of clinical trials.

Even more novel approaches include the concept of predatory bacteria or viruses, anti-bacterial chemicals derived from amphibians or reptiles, gene editing and metal nano-particles of copper or silver. All of these could help to reduce our reliance on antibiotics.

Meanwhile bioengineered “medical” honey, which works by a focused release of oxygen into the affected area, has also seen promising results in healing serious infections.

But whatever the outcome of the current spate of research, the watchful eye of front-line clinicians will remain crucial in the continuing fight against antimicrobial resistance.

For, as Irish economist Professor Cormac Ó Gráda notes, “The war against microbes is a war against Darwinian evolution: the point is not to win but to stay ahead.”