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Widening scope to tackle antimicrobial resistance

In June the public selected antibiotic resistance to be the focus of the Longitude Prize 2014. This £10m prize fund is calling for a new and innovative point of care toolkit that will help combat the growing problem of antibiotic resistance. Anna Williams, researcher on the project, explains.

Antibiotics have revolutionised medicine, adding an average of 20 years to each person’s lifetime. Penicillin alone has saved tens of millions of lives since its discovery 86 years ago but the efficacy of these life-saving drugs is threatened by the evolution of resistant bacteria. This resistance is caused in part by human behaviour and prescription practices. The G8 Science Ministers’ meeting in June 2013 identified antimicrobial resistance as “humanity’s most pressing concern, transcending national boundaries and posing significant threats to societies and ecosystems”.

Taking action: Widening scope for stewardship

The effects of antimicrobial resistance on the NHS can already be seen in efforts to tackle Methicillin-resistant Staphylococcus aureus (MRSA) and C. difficile. These resistant healthcare associated infections caused thousands to die at the peak of the outbreak. In 2007, C. difficile caused 8,324 deaths in the UK.

Through better control of antibiotic prescribing, handwashing and hygiene protocols and consistent, meticulous, intravenous central line care, outbreaks of MRSA have reduced by 84.7% between 2003 and 2011 and outbreaks of C. difficile by 53% between 2008 and 2011.

There is a large evidence base for the methods used to tackle MRSA and C. difficile. Success has come in part through mandatory surveillance and target-setting. However, our current infection control policies might not be best designed to tackle infections other than MRSA and C. difficile. With outbreaks of gram-negative healthcare associated infections on the rise, it cannot be assumed that the same methods of infection control and surveillance will be successful for these new types of resistant infection.

Gram-negative bacteria have unique features that make them harder for antibiotics to target and are also developing multi-drug resistance. They are giving rise to infections including pneumonia, wound or surgical site infections, and meningitis in healthcare settings, and now account for the majority of bloodstream infections.

Courses for action

There are two main courses of action: prevention and control of infection, and the development of novel antibiotics. However, the number of antibiotics in the development pipelines is low, and with growing incidents of multi-drug resistance organisms, stewardship of existing antibiotics is of increasing importance.

CCGs can impose financial penalties on a foundation trust that fails to reach targets for the reduction of MRSA and C. difficile infections. However, these penalties have been criticised because infection trajectories are difficult to predict, bringing into question the creation of specific targets. Financial penalties could be even less effective for gram-negative infections, for which less evidence for predicting trajectories is available.

‘Stewardship’ initiatives aim to reduce the unnecessary prescribing of all types of antibiotics. The ‘Target Toolkit’ and ‘Start Smart, Then Focus’ campaigns give guidance on antibiotic prescriptions in primary and secondary care, respectively. However, because gram-negative bacteria responds to very few classes of antibiotics, we require more than guidance on prescription practices.

Surveillance is needed in all environments where resistance can occur. As care is increasingly being delivered in the community by multiple organisations, this may lead to difficulty in implementing standards. Therefore, we require action to develop explicit infection control policies that are specific to the settings of care.

The chief medical officer commented that the NHS is well equipped to collect, collate, analyse and disseminate information from surveillance. The Department of Health has stated that the UK needs to develop methods to ensure consistency and standardisation of data collection, and this could be helped by opening up access to statistical information about infection for modelling. This work must be underpinned by common interoperability standards for health information systems so that emerging surveillance technologies can be integrated across national borders.

Point of care test kits

There is a role for innovation in diagnostics for infections to improve infection control and surveillance in the future. Current lab culture based techniques for the diagnosis of infection are slow, and require specific resources and expertise. The development of cheap, accurate and rapid point of care diagnostics will allow for the more targeted use of antibiotics. This in turn will lead to a reduction in the use of broad-spectrum antibiotics, curtailing the opportunity for resistance to occur. The impact on global levels of resistance could be far-reaching if the test was versatile and cheap enough to be used in primary and secondary care settings. Such test kits will also provide an opportunity to collect data on infection from a much greater range of care settings across the world.

The more patients get the right antibiotic prescription the first time, the longer we can preserve the action of our existing antibiotics. This is why the Longitude Prize is offering a reward fund of £10m to incentivise innovation in point of care diagnostics for infection.

Over the next five years, Nesta, with the support of the Technology Strategy Board, will be accepting and judging submissions from innovators working to produce a rapid, accurate test that has the potential to identify bacterial strains and profile possible resistance to antibiotics.

Novel innovation, both in diagnostics and the production of antibacterial agents, have to be supported by surveillance and data collection. Then we can develop an effective evidence base for techniques to control antimicrobial resistance with co-ordination at a local and national level.

The global nature of resistance means we must also find new ways to work internationally, share data and set standards for interoperability to slow this growing threat.

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