Antibacterial Perfluorocarbon Ventilation to Treat Severe Respiratory Infections

描述（由申请人提供）：在美国，急性下呼吸道感染导致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。对于严重的肺炎、慢性肺部疾病叠加的细菌感染和支气管扩张尤其如此。抗生素全氟碳通气（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，肺是

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.