AZTREONAM LYSINATE FOR INHALATION IN CYSTIC FIBROSIS PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。囊性纤维化是一种常染色体隐性遗传病，以进行性阻塞性肺疾病为特征。在美国，每年大约每2500名儿童中就有一名出生时患有CFs。据估计，美国有3万人患有这种疾病，这表明CF是一种孤儿疾病。其潜在的病理基础是囊性纤维化跨膜电导调节基因的缺陷，导致氯化钠在呼吸道上皮细胞膜上的异常移动。由此产生的异常稠密的粘液干扰了细菌和其他生物从呼吸道的粘液纤毛清除。铜绿假单胞菌是与慢性阻塞性肺疾病相关的最重要的细菌病原体。PA感染是CF自然发展过程中的一个重要事件，并与肺功能下降的比率增加有关。在所有年龄段，58%的CF患者感染了PA，到18岁时，近80%的CF患者感染了PA。某些菌株已被证明是死亡率的重要预测因子。尽管只有妥布霉素雾化吸入溶液(TOBI)获得了FDA的雾化喷雾剂使用许可，但使用羧苯西林、庆大霉素、替卡西林、妥布霉素和粘菌素雾化治疗已经研究和/或实践了很多年，5-17年。TOBI已被证明能显著改善CF患者的肺功能和其他临床参数。氨曲南是一种单杆菌类抗生素，其抗菌谱与氨基糖苷类抗生素妥布霉素和庆大霉素相似。它目前被批准用于各种严重感染的非肠道治疗。静脉注射氨曲南治疗儿童下呼吸道感染是安全有效的。PA菌株之间出现的抗生素耐药性在CF社区中是一个严重的问题，因为不受控制的PA感染会导致进行性肺部疾病。这项方案将测试另一种潜在的雾化制剂，吸入型氨曲南赖氨酸盐(AI)，它可以与其他抗生素一起用于CF患者

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis (CF) is an autosomal recessive disease characterized by progressive, obstructive pulmonary disease. Approximately one in 2,500 children in the United States each year is born with CF. An estimated 30,000 people in the United States have the disease which designates CF as an orphan disease. The underlying pathology is a defect of the Cystic Fibrosis Transmembrane Conductance Regulator gene, leading to abnormal movement of sodium chloride across respiratory epithelial cell membranes. The resultant abnormally thick mucus interferes with mucociliary clearance of bacteria and other organisms from the airways. Pseudomonas aeruginosa is the most significant bacterial pathogen associated with CF pulmonary disease. Infection with PA is an important event in the natural progression of CF and is associated with increased rates of pulmonary function decline. Across all age groups, 58% of CF patients are infected with PA, and by age 18, nearly 80% of CF patients are infected. Certain strains have been shown to be significant predictors of mortality. Therapy with aerosolized carbenicillin, gentamicin, ticarcillin, tobramycin, and colistin has been studied and/or practiced for many years, 5-17 although only tobramycin solution for inhalation (TOBI¿) has FDA licensure for aerosol use. TOBI has been shown to produce substantial improvements in pulmonary function and other clinical parameters in CF patients. Aztreonam is a monobactam antibiotic with an antibacterial spectrum similar to that of the aminoglycoside antibiotics tobramycin and gentamicin. It is currently approved as parenteral therapy for a variety of serious infections. Intravenous aztreonam has been shown to be safe and efficacious for treatment of lower respiratory tract infections in children with CF. Emergence of antibiotic resistance among PA strains is a serious concern within the CF community because uncontrolled PA infections contribute to progressive lung disease. This protocol will test another potential aerosolized agent, inhaled aztreonam lysinate (AI), which could be used with other antibiotics in CF patients