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

洗必泰(CHG)和其他双双胍在临床环境中是用于皮肤部位、导管和其他医疗植入物消毒的重要试剂。在所有这些情况下，生物膜的形成都与负面临床结果有关，部分原因是生物膜对所使用的抗菌剂提供了保护。近年来，假单胞菌和耐甲氧西林金黄色葡萄球菌等病原体对CHG的敏感性降低，加剧了生物被膜带来的挑战。这种敏感性的降低是通过增加外排泵活性来调节的，这可以防止所需的CHG浓度在细菌细胞内积累。存在一些有效的外排泵抑制剂(EPI)，但这些化合物与现有的洗必泰制剂不相容。在初步研究中，一组阳离子树枝状聚合物被成功地整合到洗必泰配方中，并在初步研究中显示出希望。该项目将通过调查一系列制剂对临床相关菌株生物被膜的影响来扩展这一初步数据，以开发一系列新的抗生物被膜洗必泰/EPI制剂。

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.