Antimicrobial Tracheostomy Tube to Prevent Biofilm and Reduce InfectionRisks

抗菌气管切开插管可防止生物膜并降低感染风险

• 批准号: 9904325
• 负责人: Jennifer Ann Neff
• 金额: $ 59.06万
• 依托单位: ALLVIVO VASCULAR, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-06 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904325
• 关键词: Acinetobacter baumannii; Address; Animal Model; Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Cationic Peptides; Bacteria; Bacterial Pneumonia; Cellulitis; Child; Childhood; Chronic Disease; Clinical; Data; Development; Devices; Drainage procedure; Engineering; Enteral Feeding; Family; Family suidae; Formulation; Foundations; Goals; Immune system; Infection; Licensing; Mechanical ventilation; Mechanics; Microbial Biofilms; Modeling; Morbidity - disease rate; Nosocomial Infections; Operative Surgical Procedures; Patients; Peptides; Performance; Phase; Polymers; Primary Infection; Procedures; Process; Pseudomonas aeruginosa; Quality of life; Resistance; Respiratory Therapy; Respiratory Tract Infections; Risk; Safety; Sterilization; Stomas; Streptococcus pneumoniae; Testing; Tracheitis; Tracheostomy Tube; Tracheostomy procedure; Tracheotomy procedure; Treatment Cost; Tube; Tympanostomy; Voice Prostheses; Work; antimicrobial; antimicrobial peptide; asparaginase; bacterial resistance; base; biomaterial compatibility; cost; cytotoxicity; drug resistant bacteria; efficacy study; endotracheal; hospital readmission; hydrophilicity; improved; in vitro activity; in vivo; innovation; meetings; methicillin resistant Staphylococcus aureus; mortality; multi-drug resistant pathogen; novel; pathogen; pediatric patients; pre-clinical; preclinical efficacy; preclinical safety; premature; preservation; prevent; recurrent infection; safety study; success; ventilator-associated pneumonia

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.

抽象的 该应用的目的是开发抗菌气管切开术管（TT）以减少感染 与气管施加剂和延长的机械通气（PMV）相关。大约100,000名患者 在美国，每年一次进行气管切开术。1大约5000例患者是儿童，使其成为其中之一 最常见的小儿外科气道程序。2儿童的气管阶层数量有所增加 近年来，预计近年来将继续上升，这主要是由于 孩子过早出生，患有慢性疾病。与气管切开术相关的感染很常见，并且 包括造口纤维炎，气管炎和肺炎细菌，包括呼吸机相关肺炎（VAP）。 在接受气管切开术并用TT出院的儿童中，有17％的人计划外 在30天内的医院再入院，并在一年内重新入院，以便在一年内重新入院。 相关呼吸道感染（Btarti）.3，4个生物膜在TTS和港口细菌上迅速形成 抗抗生素和患者的免疫系统。这些生物膜有助于感染和 治疗中感染的持续性，特别是在依赖PMV的患者中。虽然有问题 与TTS上的生物膜形成相关，已经清楚地鉴定出来，今天没有抗菌TTS 可用的。我们假设防止在TTS上形成生物膜将提高其安全性和功能，并且 相信有很大的商业机会可以满足这种未满足的需求。 第二阶段的工作范围建立在强大的I期结果上，该结果确立了基于PVC的能力 气管试管，具有新型抗菌肽的新公式。涂层设备有效 在防止多药耐药病原体形成生物膜时，在细胞毒性研究中是生物相容性的。 涂层的ETT还显示出机械耐用，并且在绝育后保持稳定/活跃。 II期对象包括（1）优化涂料公式，（2）开发飞行员秤涂料过程 要求，（3）评估大型动物模型中的安全性和效率，（4）完成生物相容性和 台式测试，以及（5）与FDA完成预审会议。 预计该项目的成功将对的安全和生活质量产生重大影响 通过预防呼吸机相关的肺炎和计划外，气管验证的患者及其家人 由于呼吸道感染而导致的医院再入院。这具有降低治疗成本的高潜力。它 还可以减少需要抗生素治疗的患者数量，并以这种方式有助于保持效率 前线临床抗生素。