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: 8377155
• 负责人: Keith E Cook
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8377155
• 关键词: Acute; Alveolar; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Therapy; Antibiotics; Area; Bacterial Infections; Breathing; Bronchiectasis; Cessation of life; Characteristics; Chronic lung disease; Data; Deposition; Disease; Effectiveness; Emulsions; Environmental air flow; Excision; Fluorocarbons; Future; Gases; Goals; Healed; Hour; In Vitro; Infection; Inflammation; Liquid Ventilation; Liquid substance; Liver; Lung; Lung Inflammation; Microbial Biofilms; Modeling; Morbidity - disease rate; Mucociliary Clearance; Mucous body substance; Outpatients; Patients; Pneumonia; Property; Pseudomonas aeruginosa; Rattus; Respiratory Tract Infections; Source; Spleen; Surface Tension; Techniques; Tobramycin; Toxic effect; Treatment Cost; Ventilator; base; direct application; experience; healing; improved; mortality; mucoid; respiratory

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. PUBLIC HEALTH RELEVANCE: This project will determine if antibacterial perfluorocarbon ventilation (APV) can improve treatment of severe bacterial lower respiratory infections. APV is intended as an adjunct therapy to systemic or inhaled antibiotics. It utilizes a tidal flow of perfluorocarbon (PFC) containing emulsified antibiotics to actively wash infected mucus from the lungs, deposit antibiotics directly at the infection, and reduce lung inflammation due to a reduced bacterial load and inherent anti-inflammatory properties of PFCs.

描述（由申请人提供）：急性下呼吸道感染引起的疾病和死亡比美国的任何其他感染都要多。在大多数情况下，细菌感染接受了全身或吸入的抗生素治疗。但是，大量患者仍然患有严重的发病率和死亡率严重感染，可以从改进的治疗技术中受益。对于严重的肺炎，细菌感染叠加在慢性肺部疾病状态和支气管扩张症上，尤其如此。如果用作传统的全身或吸入抗生素疗法的辅助手段，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，肺是 用含有乳化的抗生素的全氟化合物液体（PFC）进行潮汐通风，最多几个小时。该技术可以通过多种方式加速标准的抗生素疗法。首先，PFC的潮流积极地消除了由于剪切和粘液表面张力减少而导致气道壁感染的粘液。然后将粘液从肺部从肺部进行对流运输，并通过浮力辅助，并轻松从PFC呼吸机中移走。其次，将抗生素直接递送到感染来源，从而使HE肺浓度更高，并且全身浓度和毒性较低。但是，与吸入的抗生素治疗不同，只能将抗生素提供给有效气体通风的区域，PFC中抗生素的对流运输将使更均匀的分布降至肺泡水平。有效的粘液去除还应允许抗生素在APV期间和使用吸入抗生素治疗期间更容易获取先前塞的气道。最后，PFC具有抗炎性特性，可促进肺部愈合并恢复正常的粘膜纤毛清除率。最终，APV可能会降低因严重呼吸道感染而导致的发病率，死亡率和治疗成本。为了建立APV的有效性，我们将用粘液铜铜鼠感染大鼠。然后，我们将与单独吸入毒素的治疗方法进行比较，2）全氟化合物通气，然后吸入毒霉素，3）用乳化毒素的耐二氟霉素的全氟化合物通气，然后浸入了耐甲状腺素，或4）耐荧光的耐荧光量和耐荧光素的供应。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的数据和指导，以寻求通过检查不同的通风环境和乳液特征来优化治疗。 公共卫生相关性：该项目将确定抗菌全氟碳通气（APV）是否可以改善严重细菌下呼吸道感染的治疗。 APV旨在作为全身或吸入抗生素的辅助疗法。它利用了含有乳化抗生素的全氟化合物（PFC）的潮流，从肺部积极洗涤感染的粘液，直接在感染处沉积抗生素，并减少由于细菌载荷减少和PFCS固有抗抑制性能而导致的肺部炎症。