SBIR Phase I: Preventing Biofilms on Indwelling Medical Devices with Novel Anti-Biofilm Small Molecules

这个小型企业创新研究(SBIR)第一阶段项目描述了一种减少与留置医疗器械相关的感染的新方法。医疗器械上的细菌特别难治疗，因为它们在医疗器械的表面形成了一种名为生物膜的保护基质。在生物膜状态下很难接触到细菌，全身使用抗生素通常对生物膜中的细菌无效。我们发现了一类新颖的小分子，它可以抑制细菌形成生物膜的能力，也可以分散预先形成的细菌生物膜。据报道，这是唯一一类能够分散革兰氏阳性和革兰氏阴性细菌预先形成的生物膜的小分子。在医疗器械上发现了革兰氏阳性和革兰氏阴性细菌生物膜。对于第一阶段的SBIR，我们建议测试通过共价键合技术将我们的抗生物膜化合物引入医疗器械的可行性。该项目的广泛影响/商业潜力解决了与医疗器械感染有关的健康和经济负担。在美国，留置医疗器械每年与大约100万例感染和5万例死亡有关，每年花费数亿美元治疗这些感染。此外，与留置医疗器械有关的感染目前约占所有医院获得性感染的一半。据估计，每年消除已知与设备生物膜有关的感染的直接成本约为6.5亿美元。

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.