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、未得到解决的传染病，发生在需要机械通气的气管插管患者中。在美国，每年有160万名L患者需要机械通气，其中15%-25%会患上呼吸机相关性肺炎，24%-71%会死于这种疾病。此外，VAP每年给美国医疗行业造成12亿美元的损失。VAP的一个主要原因是气管内管内微生物和微生物生物膜的增殖，在机械通气过程中，微生物和微生物生物膜被移位到肺内，导致气管支气管炎和肺炎。 拟议的SBIR-AT-NIAID项目的主要目标是进行一项受控、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)减少气管内微生物和相关生物膜的安全性和有效性。预计气管内微生物的减少将显著降低VAP的发生率，降低发病率、死亡率、住院时间和总治疗费用。 光动力疗法是一种结合使用光敏化溶液和光来产生氧自由基，从而破坏微生物的治疗方式。先进光动力技术公司开发和优化了一种PDT系统，该系统在体外、体外和体内实验中已被证明在广谱根除抗药性病原体、真菌和生物膜方面是有效的。此外，建议的光敏剂溶液和光组合的安全性已经在GLP控制的大型哺乳动物研究中得到证实。这项拟议的临床研究将证明PDT治疗作为一种减少气管导管生物被膜从而降低VAP发生率的方法的安全性和有效性。建议的PDT系统的独特之处在于，目前还没有有效的替代治疗气管内管微生物生物膜用于临床。

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.