Medical devices that bacteria can’t grip
It is not a happy image: communities of bacteria on the surfaces of urinary catheters, encased in a protective ‘slime’ that makes them 1,000 times more resistant to the body's natural defences and systemic antibiotics.
But this is the stark daily reality facing our hospitals. Urinary tract infections from catheters account for 38% of all healthcare associated infections (HAIs). This poor outcome for patients also brings a huge cost to the NHS in additional unplanned care and resources. In fact, just a 10% reduction in HAIs in the UK would save the health service more than £93 million a year.
It was in 2012 that a team from the Schools of Pharmacy and Life Sciences at the University of Nottingham first discovered a bacteria-resistant material using Wellcome Trust funding. Six years on, the project took the groundbreaking discovery and translated it into a CE-certified, bacteria-resistant catheter. These are now undergoing large scale, multi-site clinical trials with Camstent Ltd, after promising first-in-human data.
Morgan Alexander, Professor of Biomedical Surfaces, led the team that made the crucial discovery.
"This has gone all the way from a discovery of a new class of materials to clinical trials, and that’s a massive achievement. The CE mark is for urinary catheters only, but we have had a lot of interest from companies who manufacture other medical devices. This is an exciting time."
The original discovery was aided by approaching the problem from a different angle. Others had tried to search for polymer coatings that would kill bacteria. Paul Williams, Professor of Molecular Microbiology, says the team thought differently by asking “what kind of surface would bacteria not like?”
They went on to discover a new group of structurally related polymers that prevent infection by stopping the formation of biofilm on the surface, at the earliest possible stage. This is when bacteria attempt to stick irreversibly to the catheter.
They made the discovery with the help of experts from the Massachusetts Institute of Technology (MIT) who developed a process for screening thousands of polymers simultaneously. Professor Paul Williams describes the result as “a bit of a bacterial Teflon”; a non-stick surface that bacteria won’t latch on to.
In 2012, the University published a major paper in Nature Biotechnology. It generated considerable interest, but a proposal that stood out came from a small and recently formed manufacturer of catheters – Camstent – based in Cambridge.
Professor Morgan Alexander says: “Between our team discovering this material and Camstent developing a coated catheter, there was a host of important optimisation experiments.” A major advantage was that the engineering expertise required was available ‘in-house’, with Derek Irvine, Professor of Materials Chemistry, coming on board. He recalls: “A lot of the work we did initially was trying to define polymer formulations that would give the level of flexibility needed to handle a catheter without actually damaging the coating.”
"Anyone who has a catheter for longer than a week is likely to get an infection."
Once the team was satisfied that they had achieved that flexibility while still retaining antibacterial properties, CE approval was the next goal, opening the door to trials on patients. Dr Dave Hampton, Chief Technical Officer at Camstent, says: “As well as rigorous safety tests, the production process had to be tested, to ensure there were no faults in manufacture and that devices stay sterile in their packaging. We are now very confident we have reached the stage where patients will benefit, and are excited to see the results of the trials.”
These trials are being held in six hospitals across the UK, and have attracted leading medical and surgical urologists across the UK. Catheters used in the trials will be returned to Professor Williams and his team to examine for signs of biofilm formation. The tests will help determine whether promising lab results translate into a significant reduction in infection rates, costs and unplanned care. The National Institute for Health and Care Excellence (NICE) will carry out the economic analysis.
Professor Williams concludes: “Millions of urinary catheters are used every week around the world, and anyone who has a catheter for longer than a week is likely to get an infection. These materials could be a major breakthrough.”
Professor Alexander continues to look for answers. “We know how these materials work, but the more complex question is why they work. If we can understand the mechanisms, we can expand the application of these polymers.”
The ability to foil bacteria opens up many other avenues. The team is currently evaluating possibilities ranging from endotracheal tubes that help patients breathe, to cochlear implants, prosthetic joints and dental products.
Morgan Alexander is a Professor of Biomedical Surfaces in the School of Pharmacy. His group develops materials for application in biological environments, characterising relationships between the surface and biological response.
Paul Williams is a Professor of Molecular Microbiology in the School of Life Sciences. His research interests focus primarily on the regulation of gene expression in bacteria through cell-cell communication (quorum sensing) and the development of novel antibacterial agents and bacterial attachment resistant polymers.
Derek Irvine is a Professor of Materials Chemistry in the Department of Chemical and Environmental Engineering. His expertise in polymers and their industrial applications includes 16 years in research posts at ICI.