Antimicrobial Tracheostomy Tube to Prevent Biofilm and Reduce InfectionRisks

摘要 这项应用的目标是开发一种抗菌气管切开管(TT)，以减少感染 与气管切开和长时间机械通气(PMV)相关。大约100,000名患者 每年在美国接受气管切开术1.这些患者中约有5000名是儿童，使其成为 最常见的儿科外科呼吸道手术2.儿童气管切开术的数量有所增加 近几年大幅增加，预计将继续上升，主要是由于 早产和患有慢性病的儿童。与气管切开相关的感染很常见， 包括吻合口蜂窝织炎、气管炎和细菌性肺炎，包括呼吸机相关性肺炎(VAP)。 在接受气管切开术并在TT到位的情况下出院的儿童中，17%的儿童有计划外 30天内再次入院，超过40%在一年内因细菌气管造口术再次入院 相关呼吸道感染(TARTI)。3、4生物膜在TTS上迅速形成，并含有 对抗生素和患者的免疫系统产生抗药性。这些生物膜有助于感染和 持续接受治疗的感染，特别是依赖PMV的患者。尽管存在问题 与生物膜形成相关的TTS已被明确识别，目前还没有抗菌剂TTS 可用。我们推测，阻止TTS上生物被膜的形成将提高TTS的安全性和功能性，并 相信有一个巨大的商业机会来满足这一未得到满足的需求。 第二阶段的工作范围建立在第一阶段结果的基础上，该结果确立了涂覆聚氯乙烯的能力 使用一种新型的工程抗菌肽配方的气管导管。有涂层的装置是有效的 在防止多重耐药病原体的生物被膜形成方面，并且在细胞毒性研究中具有生物相容性。 涂层ETT也被证明是机械耐用的，并在灭菌后保持稳定/活性。 第二阶段的目标包括(1)优化涂料配方，(2)开发中试规模的涂料工艺 要求，(3)在大型动物模型中评估安全性和有效性，(4)完成生物相容性和 平台测试，以及(5)完成与FDA的提交前会议。 该项目的成功预计将对以下人员的安全和生活质量产生重大影响 预防呼吸机相关性肺炎和计划外肺炎的气管切开患者及其家属 因呼吸道感染再次入院治疗。这对降低处理成本具有很大的潜力。它 还可以减少需要抗生素治疗的患者数量，并通过这种方式帮助保持疗效 一线临床抗生素。

ABSTRACT The goal of this application is to develop an antimicrobial tracheostomy tube (TT) to reduce infections associated with tracheostomies and prolonged mechanical ventilation (PMV). Approximately 100,000 patients undergo a tracheotomy each year in the US.1 About 5000 of these patients are children, making it one of the most common pediatric surgical airway procedures.2 The number of tracheostomies in children has increased substantially in recent years and is expected to continue to rise, largely due to an increase in survival of children born prematurely and with chronic disorders. Tracheostomy related infections are common and include stoma cellulitis, tracheitis, and bacterial pneumonia, including ventilator associated pneumonia (VAP). In children that receive a tracheostomy and are discharged with a TT in place, 17% have an unplanned hospital readmission within 30 days and over 40% are readmitted within one year for bacterial tracheostomy associated respiratory tract infection (bTARTI).3, 4 Biofilms form rapidly on TTs and harbor bacteria that are resistant to antibiotics and the patient’s immune system. These biofilms contribute to infections and the persistence of infections under treatment, especially in patients dependent on PMV. Although problems associated with biofilm formation on TTs have been clearly identified, today there are no antimicrobial TTs available. We hypothesize that preventing biofilm formation on TTs will improve their safety and function and believe that there is a substantial commercial opportunity to address this unmet need. The Phase II scope of work builds on strong Phase I results that established the ability to coat PVC based tracheal tubes with a novel formulation of an engineered antimicrobial peptide. Coated devices were effective at preventing biofilm formation by multidrug resistant pathogens and were biocompatible in cytotoxicity studies. The coated ETTs were also shown to be mechanically durable and remained stable/active post sterilization. Phase II objectives include (1) optimizing the coating formulation, (2) developing pilot scale coating process requirements, (3) evaluating safety and efficacy in a large animal model, (4) completing biocompatibility and bench testing, and (5) completing a pre-submission meeting with FDA. Success of this project is expected to have a significant impact on the safety and quality of life of tracheostomized patients and their families by preventing ventilator associated pneumonia and unplanned hospital readmissions due to respiratory tract infections. This has high potential to reduce treatment cost. It may also reduce the number of patients requiring antibiotic therapy and, in this way, help preserve the efficacy of front line clinical antibiotics.