Photodynamic Treatment of Endotracheal Tube Biofilms

描述（由申请人提供）： 呼吸机相关性肺炎（VAP）是一种常见的、严重的、危及生命的和未解决的感染性疾病问题，发生在使用气管插管插管并需要机械通气的患者中。在美国每年需要机械通气的160万患者中，15-25%将发展VAP，24-71%将死于该疾病。此外，VAP每年使美国医疗保健行业损失12亿美元。VAP的一个主要原因是微生物和微生物生物膜在气管内导管内部的增殖，其在机械通气期间移位到肺中，导致气管支气管炎和肺炎。 拟议SBIR-AT-NIAID项目的主要目的是进行一项受控、双臂、多机构IRB批准的人体临床试验，以确定使用光动力疗法（PDT）减少气管插管微生物和相关生物膜的安全性和有效性。气管内导管微生物的减少预计将导致VAP的发生率显著降低，发病率、死亡率、住院时间和总治疗费用降低。 PDT是一种治疗方式，其结合使用光敏溶液和光来产生氧自由基，从而导致微生物的破坏。Advanced Photodynamic Technologies，Inc.已经开发和优化了PDT系统，该系统已被证明在体外，离体和体内实验期间有效地广谱根除抗生素耐药致病菌，真菌和生物膜。此外，已在GLP对照大型哺乳动物研究中确定了拟定光敏剂溶液和光组合的安全性。拟议的临床研究将证明PDT治疗作为减少气管插管生物膜的一种手段的安全性和有效性，从而降低VAP的发生率。申报的PDT系统的独特之处在于，目前临床上还没有气管插管微生物生物膜的有效替代治疗方法。

DESCRIPTION (provided by applicant): Ventilator-associated pneumonia (VAP) is a common, significant, life threatening and unaddressed infectious disease problem that occurs in patients who are intubated with an endotracheal tube and require mechanical ventilation. Of the l .6 million patients per year in the US who require mechanical ventilation, 15-25% will develop VAP and 24-71% will die of the disease. In addition, VAP costs the US healthcare industry $1.2 billion dollars annually. A major cause of VAP is the proliferation of microorganisms and microbial biofilm on the interior of the endotracheal tube, which during mechanical ventilation is dislodged into the lung resulting in tracheobronchitis and pneumonia. The primary objective of the proposed SBIR-AT-NIAID project is to perform a controlled, double armed, multi-institutional IRB approved human clinical trial to determine the safety and efficacy of using Photodynamic Therapy (PDT) to reduce endotracheal tube microorganisms and associated biofilm. The reduction of the endotracheal tube microorganisms is expected to result in a significant reduction of the incidence of VAP with reduced morbidity, mortality, length of hospital stay and overall cost of treatment. PDT is a treatment modality that combines the use of a photosensitizing solution and light to create oxygen radicals resulting in the destruction of microorganisms. Advanced Photodynamic Technologies, Inc. has developed and optimized a PDT System that has been proven to be effective in the broad spectrum eradication of antibiotic resistant pathogenic bacteria, fungi and biofilms during in vitro, ex vivo and in vivo experiments. In addition, the safety of the proposed photosensitizer solution and light combination has been established in a GLP controlled large mammal study. The proposed clinical study will demonstrate the safety and efficacy of PDT treatment as a means to reduce endotracheal tube biofilm resulting in a reduction in the incidence of VAP. The proposed PDT System is unique in that no effective alternative treatment of endotracheal tube microbial biofilms is currently available for clinical use.