Currently, about 10% of the hospital patients in the United States receive indwelling urinary catheters, and these catheters lead to over 400,000 cases per year of catheter-associated urinary tract infections. In addition, these catheter irritate urethral surfaces, causing pain upon insertion, lesions after prolonged use, and enhanced colonization of the urethral surfaces by bacteria. Administration of antibiotics is often an ineffective treatment; prevention is the most promising approach to decreasing device-associated microbial infections. One approach to preventing bacterial colonization is by attaching microbicidal agents to the device prior to implantation. Bio-Metric Systems, Inc., has successfully derivatized, purified, and covalently immobilized an antimicrobial peptide to polystyrene and performed preliminary assessments of the retained microbicidal activities. The peptide used in this study, magainin, has broad spectrum activity against a variety of commonly occurring infectious organisms. Proof-of- concept for the effectiveness of magainin was demonstrated by preparing modified surfaces that resist colonization of Staphylococcus epidermidis and Escherichia coli, as tested in vitro. In this proposed project, we plan to optimize the immobilization chemistry and explore the microbicidal activity of coated urinary tract cathcter materials in vitro. Specific Phase I objectives are to utilize rubber latex and silicone rubber urinary catheters (as the two most commonly used catheter materials) and: 1) immobilize antimicrobial peptide onto each catheter type; 2) measure inhibition of bacteria colonization; and 3) begin developing procedures to incorporate lubricious coatings as well as microbicidal reagents on substrate surface. Phase II studies will include in vitro and in vivo assays for antimicrobial activity, lubricity, tissue damage and deposition of encrusting materials.
