A NOVEL BIS-INDOLE COMPOUND AGAINST CATHETER COLONIZATION

DESCRIPTION (provided by applicant): Infections associated with medical devices can be serious and even fatal. Catheter colonization and production of a biofilm on the surface of a catheter shortly after implantation are normally the prelude for infections. A number of antimicrobial-treated catheters have been developed to combat these infections, however, many of them have limited clinical efficacy. Thus, the prevention of catheter-associated infections remains a major unmet medical need. To combat this problem, we have developed an innovative catheter coating that has been shown to be effective in preventing catheter colonization by Gram-positive and Gram-negative pathogens. The innovative catheter coating consists of MBX-1631, a novel broad-spectrum antimicrobial agent that was developed by Microbiotix, Inc. The overall goal of the proposed research is to develop antimicrobial coatings for medical devices that will prevent device-associated infections. In Phase I, we will formulate device coatings containing MBX-1631 and several analogs, and we will use them to coat medical device materials. The anti-biofilm properties and cytotoxicity of these coated devices will be tested in a series of in-vitro assays to evaluate their efficacy and selectivity. In addition, the several physical parameters of the coated devices, such as elution kinetics and durability, will be evaluated. Finally, selected coated devices will be evaluated in animal models to test for their antimicrobial efficacy and toxicity. Compounds thatmeet specified criteria for efficacy, selectivity, and physical properties will be developed further in Phase II. In Phase I we will accomplish the following specific aims: Aim 1. Formulate and apply catheter coatings consisting of MBX-1631 and several analogs; Aim 2. Evaluate the efficacy in preventing bacterial colonization, selectivity, and physical properties of coated materials using in-vitro assays; Aim 3. Evaluate efficacy and selectivity of coated materials in animal models of foreign body infection and acute toxicity. PUBLIC HEALTH RELEVANCE: Over 5 million vascular catheters are inserted in patients every year, and about 5% of these catheters lead to catheter-associated infections. Bacterial pathogens that colonize catheters and produce a biofilm on the surface of the catheter shortly after implantation are the cause of catheter-associated infections. A number of antimicrobial-treated catheters have been developed to combat these infections; however, many of them are not effective against biofilms. To combat this problem, we will develop an innovative catheter coating that has been shown to be effective in preventing catheter colonization by Gram-positive and Gram-negative pathogens.