Inhibition of Biofilms on Tympanostomy Tubes

鼓膜造口管上生物膜的抑制

• 批准号: 7910207
• 负责人: Ted W Reid
• 金额: $ 15.54万
• 依托单位: SELENIUM, LTD
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-05 至 2011-12-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910207
• 关键词: Acute; Adverse effects; Animal Model; Bacteria; Bacterial Adhesion; Bacteriocides; Binding; Candida albicans; Cells; Child; Clinical; Complication; Development; Devices; Ear; Gold; Half-Life; Implant; In Vitro; Marketing; Methods; Microbial Biofilms; Modeling; Operative Surgical Procedures; Oral cavity; Orthodontic; Otitis Media; Otitis Media with Effusion; Otorrhea; Patients; Piperacillin-Tazobactam; Prevention; Reaction; Recurrence; Resistance; Selenium; Selenium Compounds; Silicones; Solutions; Superoxides; Surface; Temperature; Test Result; Testing; Therapeutic; Time; Tube; Tympanostomy; Tympanostomy Tube Insertions; antimicrobial; base; disilver oxide; effusion; hearing impairment; killings; medical implant; operation; pathogen; pathogenic bacteria; prevent; public health relevance; standard care

DESCRIPTION (provided by applicant): Bacterial biofilm formation on medical implants is a serious clinical problem. Biofilms can turn a simple implant into a serious complication. Recently we showed that the covalent attachment of micrograms of organo-selenium to the surface of an orthodontic device will inhibit the formation of a biofilm without harmful side-effects. This has recently (2009) led to FDA approval for selenium coated orthodontic devices that can be placed into children's mouths. These devices are now on the market. The use of selenium to block bacterial biofilms is based upon the unique ability of certain organo-selenium compounds to be covalently attached to a material and yet still retain their ability to catalytically generate superoxide radicals on the surface. However, due to the short half-life of superoxide radicals, there are no effects on cells near the device. This reaction continues for as long as selenium remains attached to the device. Tests show that the selenium coating is still fully active after 3 months of soaking at an elevated temperature. Selenium inhibits gram negative and gram positive pathogenic bacteria as well as Candida albicans. The current application is based upon our recent findings that specific organo- selenium compounds can be attached to silicone tympanostomy tubes resulting in the inhibition of biofilm formation in vitro. Thus, the following specific aims are proposed: 1. To develop a pilot scale method to coat tympanostomy tubes with organo-selenium and test the resulting product in vitro against isolates obtained from otitis media patients. 2. To develop and test selenium coated tympanostomy tubes in an animal model for their ability to inhibit biofilm formation and persistent otorrhea. . PUBLIC HEALTH RELEVANCE: While tympanostomy tubes are the gold standard for treatment of otitmis media and effusion, their occlusion rate is between 11 and 25%, and otorrhea occurs in 15-50% of tube inserted ears. It is felt that biofilms forming on the tube material is the main factor in the development of otorrhea and tube occlusion. Based upon our findings that a covalent selenium coating will block biofilm formation on tympanostomy tubes, we propose testing selenium-coated tympanostomy tubes for their ability to inhibit tube occlusion and otorrhea.

描述（由申请人提供）：医疗植入物上的细菌生物膜形成是一个严重的临床问题。生物膜可以把一个简单的植入物变成一个严重的并发症。最近，我们发现，将微克有机硒共价连接到正畸装置的表面将抑制生物膜的形成，而没有有害的副作用。最近（2009年），FDA批准了可放入儿童口中的硒涂层正畸装置。这些设备现在已经上市。使用硒来阻断细菌生物膜是基于某些有机硒化合物共价连接到材料上的独特能力，但仍保留其在表面上催化产生超氧化物自由基的能力。然而，由于超氧自由基的半衰期较短，对设备附近的细胞没有影响。只要硒仍然附着在设备上，该反应就会继续。测试表明，在高温下浸泡3个月后，硒涂层仍然完全活性。硒抑制革兰氏阴性和革兰氏阳性致病菌以及白色念珠菌。本申请是基于我们最近的发现，即特定的有机硒化合物可以附着到硅胶鼓膜造口管上，导致体外生物膜形成的抑制。因此，提出了以下具体目标：1。开发一种中试规模的方法，用有机硒涂覆鼓膜造孔管，并在体外测试所得产品对中耳炎患者分离株的抗感染能力。 2.在动物模型中开发和测试硒涂层鼓膜造孔管抑制生物膜形成和持续性耳畸形的能力。. 公共卫生关系：虽然鼓膜造孔管是治疗中耳炎和积液的金标准，但其闭塞率在11%至25%之间，并且在15%至50%的插管耳中发生耳炎。我们认为，生物膜形成的管材料是主要因素，在发展中的耳畸形和管闭塞。基于我们的研究结果，共价硒涂层将阻止鼓膜造口管上的生物膜形成，我们建议测试硒涂层鼓膜造口管抑制管闭塞和耳畸形的能力。