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
基本信息
- 批准号:8377155
- 负责人:
- 金额:$ 7.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcuteAlveolarAnti-Bacterial AgentsAnti-Inflammatory AgentsAnti-inflammatoryAntibiotic TherapyAntibioticsAreaBacterial InfectionsBreathingBronchiectasisCessation of lifeCharacteristicsChronic lung diseaseDataDepositionDiseaseEffectivenessEmulsionsEnvironmental air flowExcisionFluorocarbonsFutureGasesGoalsHealedHourIn VitroInfectionInflammationLiquid VentilationLiquid substanceLiverLungLung InflammationMicrobial BiofilmsModelingMorbidity - disease rateMucociliary ClearanceMucous body substanceOutpatientsPatientsPneumoniaPropertyPseudomonas aeruginosaRattusRespiratory Tract InfectionsSourceSpleenSurface TensionTechniquesTobramycinToxic effectTreatment CostVentilatorbasedirect applicationexperiencehealingimprovedmortalitymucoidrespiratory
项目摘要
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):在美国,急性下呼吸道感染引起的疾病和死亡比任何其他感染都多。在大多数情况下,细菌感染用全身或吸入抗生素治疗。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。对于肺炎、细菌感染叠加慢性肺病状态和支气管扩张的严重病例尤其如此。抗生素全氟化碳通气(APV)如果作为传统全身或吸入抗生素治疗的辅助手段,可以改善严重细菌感染的治疗。在这种治疗中,
用含有乳化抗生素的全氟化碳液体(PFC)进行潮式通气,持续数小时。这项技术可以在几个方面加速标准抗生素治疗。首先,由于流体剪切和粘液表面张力降低,PFCs的潮汐流会主动从气道壁清除受感染的粘液。然后,在浮力的帮助下,粘液从肺中对流输送,并容易地从PFC呼吸机中去除。第二,抗生素被直接递送到感染源,允许在肺中的较高浓度和较低的全身浓度和毒性。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中抗生素的对流运输将允许更均匀地分布到肺泡水平。主动粘液清除还应使抗生素更容易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。最后,PFC具有抗炎特性,可能会促进肺部愈合并恢复正常的粘液纤毛清除。最终,APV可以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,我们将用粘液样铜绿假单胞菌感染大鼠。然后,我们将比较1)单独吸入妥布霉素,2)全氟化碳通气后吸入妥布霉素,3)全氟化碳通气与乳化妥布霉素,然后吸入妥布霉素,或4)全氟化碳通气与乳化妥布霉素,没有进一步的治疗。我们假设治疗后的细菌负荷和炎症将从最低到最高:组3、4、2和1。这些研究将为未来的研究提供初步数据和指导,这些研究旨在通过检查不同的通气设置和乳化特性来优化治疗。
公共卫生相关性:该项目将确定抗菌全氟化碳通气(APV)是否可以改善严重细菌性下呼吸道感染的治疗。APV预期用作全身或吸入抗生素的辅助治疗。它利用含有乳化抗生素的全氟化碳(PFC)的潮汐流来主动地从肺部冲洗受感染的粘液,将抗生素直接存款在感染处,并且由于减少的细菌负荷和PFC的固有抗炎特性而减少肺部炎症。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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Keith E Cook其他文献
Ambulatory Seven-Day Mechanical Circulatory Support in Sheep Model of Pulmonary Hypertension and Right Heart Failure.
肺动脉高压和右心衰竭绵羊模型的动态七天机械循环支持。
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
R. Ukita;Y. Patel;W. Kelly Wu;S. Francois;Michael Cortelli;Carl A Johnson;N. Cardwell;J. Talackine;J. Stokes;William Grogan;Meredith Mentz;Kaitlyn M Tracy;Timothy R Harris;William Tucker;E. Simonds;C. Demarest;Keith E Cook;D. Skoog;E. Rosenzweig;M. Bacchetta - 通讯作者:
M. Bacchetta
Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump.
使用轻型轴流泵的新型动态肺辅助系统的血液相容性评估。
- DOI:
10.1097/mat.0000000000002227 - 发表时间:
2024 - 期刊:
- 影响因子:4.2
- 作者:
Yeahwa Hong;Suji Shin;Umar Nasim;Kalliope Roberts;A.S. Potchernikov;Kimberly Y Liu;Keith A Dufendach;D. Skoog;Matthew Bacchetta;Keith E Cook - 通讯作者:
Keith E Cook
Keith E Cook的其他文献
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{{ truncateString('Keith E Cook', 18)}}的其他基金
Combined Use of Polycarboxybetaine Coatings with a Selective FXIIa Inhibitor to Create Potent Biomaterial Anticoagulation Without Bleeding During Extracorporeal Life Support
聚羧基甜菜碱涂层与选择性 FXIIa 抑制剂的组合使用可在体外生命支持期间产生有效的生物材料抗凝作用而不会出血
- 批准号:
10444025 - 财政年份:2022
- 资助金额:
$ 7.78万 - 项目类别:
Combined Use of Polycarboxybetaine Coatings with a Selective FXIIa Inhibitor to Create Potent Biomaterial Anticoagulation Without Bleeding During Extracorporeal Life Support
聚羧基甜菜碱涂层与选择性 FXIIa 抑制剂的组合使用可在体外生命支持期间产生有效的生物材料抗凝作用而不会出血
- 批准号:
10743109 - 财政年份:2022
- 资助金额:
$ 7.78万 - 项目类别:
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:
8461511 - 财政年份:2012
- 资助金额:
$ 7.78万 - 项目类别:
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 - 财政年份:2012
- 资助金额:
$ 7.78万 - 项目类别:
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