Antibacterial Perfluorocarbon Ventilation to Treat Severe Respiratory Infections

抗菌全氟化碳通气治疗严重呼吸道感染

• 批准号: 8819831
• 负责人: Keith E Cook
• 金额: $ 2.43万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8819831
• 关键词: Antibacterial; Perfluorocarbon; Ventilation; Treat; Severe

DESCRIPTION (provided by applicant): Acute lower respiratory infections cause more disease and death than any other infection in the US. In most cases, bacterial infections are treated with systemic or inhaled antibiotics. However, large groups of patients still suffer from severe infections with significant morbidity and mortality and could benefit from improved treatment techniques. This is particularly true for severe cases of pneumonia, bacterial infections superimposed on chronic lung disease states, and bronchiectasis. Antibiotic perfluorocarbon ventilation (APV) could improve treatment of severe bacterial infections if used as an adjunct to traditional systemic or inhaled antibiotic therapy. In this treatment, the lung is tidally ventilated with a perfluorocarbon liquid (PFC) containing emulsified antibiotics for a perid of up to a few hours. This technique could accelerate standard antibiotic therapy in several ways. First, the tidal flow of PFCs actively removes infected mucus from airway walls due to fluid shear and reduced mucus surface tension. The mucus is then convectively transported from the lungs, aided by buoyant force, and removed easily from the PFC ventilator. Second, antibiotic is delivered directly to the source of infection, allowing for higher concentrations in he lung and lower systemic concentrations and toxicity. However, unlike treatment with inhaled antibiotics, which can only deliver antibiotics to areas of effective gas ventilation, convective transport of the antibiotic in PFC will allow much more uniform distribution down to the alveolar level. Active mucus removal should also allow antibiotics to more easily access previously plugged airways, both during APV and treatment with inhaled antibiotics thereafter. Lastly, PFC has anti- inflammatory properties that may promote lung healing and a return towards normal mucociliary clearance. Ultimately, APV may decrease morbidity, mortality, and the cost of treatment from severe respiratory infections. To establish the effectiveness of APV, we will infect rats with mucoid Pseudomonas aeruginosa. We will then compare treatment of this infection with either 1) inhaled tobramycin alone, 2) perfluorocarbon ventilation followed by inhaled tobramycin, 3) perfluorocarbon ventilation with emulsified tobramycin followed by inhaled tobramycin, or 4) perfluorocarbon ventilation with emulsified tobramycin and no further treatment. We hypothesize that bacterial load and inflammation following treatment will be from lowest to highest: group 3, 4, 2, and 1. These studies will provide preliminary data and guidance towards future studies that seek to optimize treatment by examining different ventilation settings and emulsion characteristics.

描述（由申请人提供）：在美国，急性下呼吸道感染比任何其他感染导致更多的疾病和死亡。在大多数情况下，细菌感染可以通过全身或吸入抗生素来治疗。然而，大量患者仍然遭受严重感染，发病率和死亡率很高，可以从改进的治疗技术中受益。对于严重的肺炎、慢性肺部疾病和支气管扩张的细菌感染病例尤其如此。如果作为传统全身或吸入抗生素治疗的辅助手段，抗生素全氟化碳通气（APV）可以改善严重细菌感染的治疗。在这种治疗中，肺 使用含有乳化抗生素的全氟化碳液体 (PFC) 进行潮气通气，持续时间长达数小时。这项技术可以通过多种方式加速标准抗生素治疗。首先，由于流体剪切力和降低的粘液表面张力，PFC 的潮汐流主动清除气道壁上受感染的粘液。然后，在浮力的帮助下，粘液从肺部以对流方式输送，并轻松从 PFC 呼吸机中清除。其次，抗生素直接输送到感染源，从而使肺部浓度更高，全身浓度和毒性更低。然而，与吸入抗生素治疗不同，吸入抗生素只能将抗生素输送到有效气体通气的区域，PFC 中抗生素的对流输送将允许更均匀地分布到肺泡水平。主动清除粘液还可以让抗生素更容易地进入先前堵塞的气道，无论是在 APV 期间还是之后吸入抗生素治疗期间。最后，PFC 具有抗炎特性，可以促进肺部愈合和恢复正常的粘液纤毛清除能力。最终，APV 可能会降低严重呼吸道感染的发病率、死亡率和治疗费用。为了确定 APV 的有效性，我们将用粘液铜绿假单胞菌感染大鼠。然后，我们将比较这种感染的治疗方法：1) 单独吸入妥布霉素，2) 全氟化碳通气，然后吸入妥布霉素，3) 全氟化碳通气，乳化妥布霉素，然后吸入妥布霉素，或 4) 全氟化碳通气，乳化妥布霉素，不作进一步治疗。我们假设治疗后的细菌负荷和炎症将从最低到最高：第 3、4、2 和 1 组。这些研究将为未来的研究提供初步数据和指导，通过检查不同的通气设置和乳液特性来寻求优化治疗。

项目成果

Effects of Fluorosurfactant Structure and Concentration on Drug Availability and Biocompatibility in Water-in-Perfluorocarbon Emulsions for Pulmonary Drug Delivery.

含氟表面活性剂结构和浓度对肺部药物输送全氟化碳包水乳剂中药物利用度和生物相容性的影响。

• 发表时间: 2017-12
• 影响因子: 2.4
• 作者: Orizondo, Ryan A;Nelson, Diane L;Fabiilli, Mario L;Cook, Keith E
• 通讯作者: Cook, Keith E

Effects of Emulsion Composition on Pulmonary Tobramycin Delivery During Antibacterial Perfluorocarbon Ventilation.

抗菌全氟化碳通气期间乳剂组合物对肺部妥布霉素输送的影响。

• 发表时间: 2016-06
• 作者: Orizondo, Ryan A;Fabiilli, Mario L;Morales, Marissa A;Cook, Keith E
• 通讯作者: Cook, Keith E