Biofilm polymicrobial infection-resistant implants for otologic application

说明(申请人提供)：在美国，超过四分之一的口服抗生素用于治疗急性中耳炎。鼓膜切开并插入鼓膜管已成为慢性中耳炎儿童的首选治疗方法，在美国每年售出200多万管。鼓室造口术是发达国家在全身麻醉下最常见的儿科手术。慢性鼓膜后置管术后耳漏通常难以治疗，并以听力损失和长期中耳功能障碍的形式引起显着的发病率。联合调查人员证实，慢性中耳感染是一种粘膜生物膜疾病，这可能解释了为什么中耳炎通常很难用抗生素治疗。鼓室造孔管表面的生物膜可能是鼓室造孔术后耳漏的主要因素，因此可能是反复感染的一个来源。目前鼓室造瘘管在抑制细菌附着和生物被膜形成方面效果不佳。我们发现，在批准的植入宿主聚合物中加入特定的抗菌剂/抗生素组合，可以非常有效地防止与中耳炎相关的微生物的细菌附着和生物被膜的发展。本研究的目的是开发和测试用于鼓室造瘘管植入物的生物膜耐多菌植入物。其具体目标是：1)利用新的加工方法开发具有选定的抗菌/抗生素组合的聚合物植入材料，并研究其释放动力学；2)评估细菌对中耳炎相关生物的附着和生物膜的形成；确定各种抗菌/抗生素组合的特征，以确定与浮游和生物膜抑制有关的MIC值；以及3)评估不同抗菌/抗生素组合的耳毒性/细胞毒性。这项研究的中心创新是通过使用特殊的抗菌剂组合来开发有效的植入材料，这些抗菌剂可以专门延缓生物膜的发展和最大限度地减少疾病的复发，重点是中耳炎。

DESCRIPTION (provided by applicant): Over one-quarter of all oral antibiotics is prescribed for acute otitis media in the United States. Myringotomy with tympanostomy tube insertion has become the treatment of choice for children with chronic otitis media, with more than two million tubes sold annually in the US. Tympanostomy is the most common pediatric procedure under general anesthesia in the developed world. Chronic post-tympanostomy tube otorrhea is often refractory to treatment and inflicts significant morbidity in the form of hearing loss and long-term middle ear dysfunction. The Co-investigators have confirmed that chronic middle ear infection is a mucosal biofilm disease, and this may explain why otitis media is often difficult to treat with antibiotics. Biofilm on the surface of tympanostomy tubes may be a primary factor in post-tympanostomy otorrhea, and may thus be a source of recurrent infections. Current tympanostomy tubes are ineffective in retarding bacterial attachment and biofilm development. We have discovered that a specific combination of antimicrobial/antibiotic agents incorporated in approved implant host polymers is very effective against bacterial attachment and biofilm development of organisms associated with otitis media. The goal of this study is to develop and test biofilm polymicrobial- resistant implant materials for use as tympanostomy tube implants. The Specific Aims are: 1) to develop polymeric implant materials with selected combinations of antibacterial/antibiotic agents using novel processing methods, and to study their release kinetics, 2) to evaluate bacterial attachment and biofilm development against organisms associated with otitis media, and to define the characteristics of the various antimicrobial/antibiotic combinations to determine MIC values pertaining to planktonic and biofilm inhibition, and 3) to assess the ototoxicity/cytotoxicity of the various antimicrobial/antibiotic combinations. The central innovation of this study is the development of effective implant materials by using special combinations of antimicrobial agents that could specifically retard biofilm development and minimize recurrence of disease, with emphasis on otitis media.