Research Project
8714949
DESCRIPTION (provided by applicant): Catheter-associated urinary tract infections (CAUTI) are a leading cause of hospital-acquired infections and lead to increased costs, suffering and mortality. A primary contributor to CAUTI is formation of bacterial biofilms on indwelling catheters. Biofilms are inherently resistant to most antibiotics, and once established serve as a bacterial reservoir propagating infection to other tissues. Elution of antimicrobials from catheter has been recognized as a potential means of preventing biofilm formation on catheters and reducing CAUTI. Silver and nitrofurazone-releasing catheters are currently clinical use. However, catheters releasing these antimicrobials have relatively short durations of activity, prevent biofilm development for several days and are largely ineffective against certain key pathogens. Consequently, there is an unmet need for antimicrobial catheters that prevent biofilm formation for extended periods. Therefore, we propose to develop a novel antimicrobial Foley catheter based on the use of a proprietary compound, known as CSA-13, incorporated into a highly lubricious hydrogel coating dip coated on to silicone catheters. CSA-13 is the member of the class of ceragenin compounds and is a synthetic non-peptide compound that mimics the activity of the body's own endogenous antimicrobial peptides (AMPs). Abiotic surfaces, in contrast, such as urinary catheters, lack such protection and are rapidly colonized by bacteria which form biofilms. Our prior in vitro experiments using polyurethane coatings demonstrate that CSA-13 release prevents biofilm formation for weeks and even months. Moreover, it has been shown by others that CSA-13 is active against resistant strains of E. coli and recommended its use as an active ingredient in coatings for urinary catheters. In this study, we will determine the optimal coating approach for CSA-13 release from urinary catheters, as well as the efficacy of CSA-13, by performing a number of in vitro experiments. Successful completion of this Phase I application will allow us to develop clinical prototypes for use in vivo testing. The approach outlined in this application has a high likelihood of success and can make a significant contribution to public health in an era of increasing antibiotic resistant strains of bacteria.
