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Overcoming antibiotic resistance

Published: 28 March 2019

Antibiotic resistance is one of the greatest challenges facing the world. In 2017, Public Health England estimated that, on its current trajectory, by 2050 resistance could cause 10 million deaths and cost £66 trillion worldwide each year.

The UK government’s five-year action plan and 20-year vision to contain and control antimicrobial resistance in the UK by 2040, launched in January, is a timely reminder of the global nature of the threat and the need for coordinated action.

The first response to the growing ineffectiveness of antibiotics in treating infection tends to be to ask where the new drugs are. For some time, pharmaceutical companies have been reluctant to invest in the development of antibiotics, seeing bigger returns to be made elsewhere.

Incentivising companies to develop new antibiotics is a perennial problem. So the move by the National Institute for Health and Care Excellence and NHS England to look at how companies could be paid according to the value of the medicines to the NHS, rather than the volumes sold, is welcome.

But enticing industry to develop new drugs is just one part of the bigger puzzle.

We must ensure the antibiotics we have, and any new ones developed, are used in the right way. Unless we tackle poor prescribing and overuse of antibiotics, the government’s vision will remain just that. 

Overuse in medical treatment is a major driver of antibiotic resistance. Even in a healthcare system such as the NHS, where antibiotics can only really be obtained on prescription, patients often get antibiotics that are not necessary, less targeted or given for longer than is required. A study published in February, for example, found that 80 per cent of GP prescriptions for respiratory tract infections are for longer than recommended guidelines.

Overuse in the NHS has been reduced in recent years, but only in primary care. Antibiotic use in hospitals, where the majority of broad-spectrum antibiotics are prescribed, is increasing. Halting this worrying rise requires supporting hospital clinicians to prescribe appropriately. And research has a major role to play.

Most antibiotics in use today were discovered in the 1960s and 1970s, before the role of overuse in driving resistance was properly understood. Fundamental questions about how antibiotics should best be prescribed have been left unanswered.

These questions fall into two categories. The first is determining the optimal antibiotic use in any given situation. This includes what agent or agents are most effective, whether using antibiotics in combination is better than singly, whether oral therapy is as good as intravenous, and what the best duration of treatment is. In all of these decisions, treatment outcomes need to be balanced against selection for resistance.

Often, antibiotics lead to resistance not through their effects on the bacteria they are intended to kill, but by collateral damage to those that live on us, in us and near us. Advances in DNA sequencing and analysis are starting to make it possible to track the evolution of resistance in individual patients, and with it the resistance-related harms of different treatments.

The second group of questions involve how to put this knowledge into practice in a complex system like the NHS. Implementation studies are challenging, as they involve changing human behaviour, usually with multifaceted approaches. Robust studies on how to minimise antibiotic overuse in clinical practice often need to be large, protracted and expensive.

To date, the NIHR has awarded some £121 million for research into antimicrobial resistance. The collaboration between the NIHR Clinical Research Network and the NHS allows research with global impact.

A body of investigator-led studies are addressing different questions of optimising antibiotic choices in, for example, sepsis, paediatric pneumonia and bone infection. On implementation, the NIHR-supported Antibiotic Review Kit for hospitals is a landmark study developing and evaluating measures to support prescribers to safely stop antibiotic treatment in hospitalised patients sooner than they do now. The NIHR is also recruiting NHS patients to major licensing trials of new anti-infectives and vaccines.

Central to this work is recognising that antibiotic resistance is a problem for individuals as well as populations. For too long, clinicians have thought that the effects of antibiotics on individual patients are, by and large, entirely positive.

We now know this is not the case. Clinicians need evidence from research so that they can balance the benefits of these life-saving drugs against the harm they do.

Martin Llewelyn is antimicrobial resistance lead at the NIHR Clinical Research Network

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