Light-activated antimicrobial polymers for the prevention of catheter-associated infections

Patients in hospital are often too ill to be given drugs by mouth or by injection and these have to be administered through a fine tube connected directly to a vein or artery. Also, they are often unable to urinate and so need a tube inserted directly into their bladder so that urine can drain through this into a collecting bag. Such tubes are known as catheters and are very widely used by hospitalised patients. One of the main problems with catheters is that microbes (usually from the patient's skin) inevitably stick to their surfaces where they grow to form a structure (known as a biofilm) consisting of millions of bacteria surrounded by a jelly-like material. Inside these biofilms, the microbes are protected from the body's defence systems as well as from antibiotics. Therefore, once biofilms have formed on a catheter they are very difficult to remove and they eventually cause an infection which can kill the patient. To prevent the patient dying from such an infection, the catheter often has to be removed and a new one inserted which is very unpleasant for the patient and time-consuming for medical staff. In this project we intend developing a new way of preventing such infections - this will be based on the use of light-activated antimicrobial agents (also known as photosensitisers). A photosensitiser is a chemical that has no effect on microbes in ordinary light but is 'activated' by light of a certain wavelength - this is usually provided by a small laser. The activated photosensitiser produces substances that can kill any microbes present. We intend adding a photosensitiser to the material used to make catheters and carrying out experiments to find out whether this material, when illuminated with laser light, can either stop microbes sticking to it or else actually kill them. Once we have found out the best concentration of photosensitiser to use and how much light is necessary, we will then carry out more complicated experiments in which we will use laboratory models of catheters. If our light-activated material can prevent microbes adhering or can kill them in laboratory models, then they are likely to be effective also in patients. The light source used to activate the photosensitiser would be a low-power laser similar to the laser pointers used by teachers and lecturers so making it convenient to use - it could easily be carried around by patients who are able to walk. Light from the laser would pass through optical fibres which would be connected to the catheter. We think that this approach using light-activated antimicrobial agents is an exciting, novel way of preventing infections associated with catheters and will be of great benefit to patients.

In the UK approximately 5,000 people die each year from hospital-acquired infections (HAIs). Infections associated with catheters are the most common type of HAIs and these arise because microbes adhere to the catheter surface and form biofilms. Biofilms are refractory to host defences and antimicrobial agents and infections due to them are difficult to treat / often requiring removal of the catheter and its associated biofilm. Such procedures are costly and unpleasant for the patient. The aim of this study is to determine if incorporation of a light-activated antimicrobial agent (LAAA) into catheter material can prevent adhesion of microbes to the material or can kill any microbes that do adhere. It would be difficult in 3 years to investigate the potential of such materials in all clinical situations and so we will focus on intravascular and urinary catheters - the two most widely-used applications. The most frequent causative agents of such infections are Staph. epidermidis, Staph. aureus, Pseudomonas aeruginosa and Candida albicans (for intravascular catheters), and Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Enterococcus faecalis (for urinary catheters). We will, therefore, focus on these representative organisms. Silicone is one of the most commonly used catheter materials and so will be used in the project. Toluidine blue will be used as a representative LAAA as it can kill a wide range of Gram-positive and Gram-negative bacteria, as well as Candida albicans, and is also effective when present in a cellulose acetate coating. Flow cell technology will be used to evaluate the effectiveness of toluidine blue-containing silicone at preventing adhesion of the target organisms to the material and/or killing these organisms. Having established the optimal parameters (toluidine blue concentration, light energy density and dose) required to achieve these objectives, we will then evaluate the materials in laboratory models of a catheterized bladd