This Small Business Innovation Research (SBIR) Phase I project describes a new approach for reducing infections associated with indwelling medical devices. Bacteria on medical devices are particularly challenging to treat because they form a protective matrix called a biofilm on the surface of the device. It is very difficult to access bacteria in the biofilm state, and systemic use of antibiotics is generally ineffective against bacteria in biofilms. We have discovered a class of novel small molecules that inhibits bacteria's ability to form biofilms as well as disperses pre-formed bacterial biofilms. This is the only class of small molecules reported that is able to disperse pre-formed biofilms from both gram-positive and gram-negative bacteria. Both gram-positive and gram-negative bacterial biofilms have been identified on medical devices. For this Phase I SBIR, we propose to test the feasibility of incorporating our anti-biofilm compound into medical devices through a covalent bonding technique.
The broader impact/commercial potential of this project addresses both health and economic burdens associated with infections of medical devices. Indwelling medical devices are associated with approximately 1 million infections and 50,000 deaths in the US each year, and hundreds of millions of dollars are spent annually treating these infections. Furthermore, infections associated with indwelling medical devices currently account for approximately one half of all hospital-acquired infections. It is estimated that the direct cost of eliminating infections known to be related to device biofilms is approximately $650 million each year.
This SBIR project resulted in the development of a novel material for medical implants that may have a reduced propensity for infection. In particular, molecules discovered at NC State University that effectively inhibit bacterial colonization (also known as "biofilm formation") were covalently tethered to a catheter material. The modified catheter material was shown to resist bacterial colonization in a series of in vitro assays. This project aimed to address a significant and unmet need, as hundreds of thousands of indwelling medical devices must be removed each year due to persistent infections caused by bacterial biofilms on the catheters. Agile Sciences licensed a series of proprietary and patent-protected small molecules from NC State University, called "Agilyte™". These molecules have displayed unprecedented activity toward inhibiting and dispersing bacterial biofilms. Therefore, the scope of this project was to covalently bond the Agilyte™-molecules to a catheter so that biofilms could not form on the catheter. The first technical objective of this Phase I project was to covalently bond Agile Sciences’ "Agilyte™" molelcules onto a polymethacrylate catheter material. This objective was successfully completed, and leaching studies indicated that the Agilyte™ molecules were successfully bonded to the material. The second technical objective was to test the prototype catheter for anti-biofilm activity; structural stability; and activity under biomimetic conditions. The Agilyte™ material was particularly resistant to colonization of Acinetobacter baumannii, which is an important pathogen known to be associated with device-related infections. Further optimization is required to demonstrate efficacy toward gram-positive strains of bacteria such as Staphylococcus aureus. The structural stability of the Agilyte™ polymer was similar to that of the control sample, indicating a good stability profile for the material. ?
