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

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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.