Investigation of efflux pump biocide and antibacterial resistance mitigation in organisms within biofilms

Chlorhexidine (CHG) and other bis biguanides are important agents in clinical settings for the disinfection of skin sites, catheters and other medical implants. In all these cases the formation of biofilms is associated with negative clinical outcomes in part due to the protection that biofilms provide against the antimicrobial agents employed. In recent years the challenge presented by biofilms has been exacerbated by the emergence of a reduced susceptibility to CHG amongst pathogens such as Pseudomonas sp and MRSA. this reduced susceptibility is mediated by increased efflux pump activity which prevents the required CHG concentration from accumulation within the bacterial cell. A number of effective efflux pump inhibitors (EPI) exist but these compounds have not been compatible with existing chlorhexidine formulations. In preliminary studies one group of EPIs (cationic dendritic polymers) were successfully integrated into chlorhexidine formulations and showed promise in preliminary investigations. This project will expand on this preliminary data by investigating the impact of a range of formulations against biofilms of clinically relevant isolates in order to develop a new range of anti biofilm chlorhexidine/EPI formulations.

Chlorhexidine (CHG) and other bis biguanides are important agents in clinical settings for the disinfection of skin sites, catheters and other medical implants. In all these cases the formation of biofilms is associated with negative clinical outcomes in part due to the protection that biofilms provide against the antimicrobial agents employed. In recent years the challenge presented by biofilms has been exacerbated by the emergence of a reduced susceptibility to CHG amongst pathogens such as Pseudomonas sp and MRSA. this reduced susceptibility is mediated by increased efflux pump activity which prevents the required CHG concentration from accumulation within the bacterial cell. A number of effective efflux pump inhibitors (EPI) exist but these compounds have not been compatible with existing chlorhexidine formulations. In preliminary studies one group of EPIs (cationic dendritic polymers) were successfully integrated into chlorhexidine formulations and showed promise in preliminary investigations. This project will expand on this preliminary data by investigating the impact of a range of formulations against biofilms of clinically relevant isolates in order to develop a new range of anti biofilm chlorhexidine/EPI formulations.

The primary beneficiary will be Gama Healthcare Ltd through bringing to market products that answer the requirement for antibiofilm activity with the added benefit of efflux pump resistance mitigation. These include CHG/alcohol wipes, CHG washcloths, CHG pre-operative bathing products, CHG shampoos and shampoo caps etc. There will also be additional opportunities associated with extending the application to other bisbiguanide biocides. A secondary opportunity may be developed, dependent on IP generation to licence some product variants in certain export markets, or to primary bisbiguanide producers.

There will also be a much wider impact beyond the commercial one associated with a reduction in infection rates and associated fatalities. This will have direct quality of life impacts and financial impacts through a reduction in lost working days for the patients concerned and their family members. There will also be financial savings for the NHS through a reduction in the length of hospital stays and costs associated with treatments for blood stream infections e.g. antibiotics.
The size of these impact can be seen from the fact that the estimated costs associated for those persons which acquire a healthcare associated infection is over £1 billion a year. In the US 1/4 million of blood stream infections are associated with central line contamination and the need for effective disinfection in order to prevent biofilm formation in needless connectors has been recognised by a number of authors. A secondary impact will be on the manufacturers of medical devices, having an effective biofilm treatment and prevention technology for their devices will allow a wider dissemination of their products, potentially open up options for new designs and may extend the in use lifetimes of the products concerned.