AZTREONAM LYSINATE FOR INHALATION IN CYSTIC FIBROSIS PATIENTS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 囊性纤维化（CF）是一种常染色体隐性遗传疾病，其特征是进行性阻塞性肺病。 在美国，每年大约有2,500名儿童中有一名出生时患有CF。 据估计，美国有30，000人患有这种疾病，将CF指定为孤儿疾病。 潜在的病理学是囊性纤维化跨膜传导调节基因的缺陷，导致氯化钠穿过呼吸道上皮细胞膜的异常运动。由此产生的异常粘稠的粘液干扰粘膜纤毛从气道清除细菌和其他生物体。 铜绿假单胞菌是与CF肺病相关的最重要的细菌病原体。 PA感染是CF自然进展中的重要事件，并与肺功能下降率增加相关。 在所有年龄组中，58%的CF患者感染PA，到18岁时，近80%的CF患者感染。 某些菌株已被证明是死亡率的重要预测因子。 使用羧苄青霉素、庆大霉素、替卡西林、妥布霉素和粘菌素的雾化治疗已经研究和/或实践了多年，5-17，尽管只有妥布霉素吸入溶液（TOBI）获得了FDA的气雾剂使用许可。TOBI已被证明可显著改善CF患者的肺功能和其他临床参数。 氨曲南是一种单内酰胺类抗生素，其抗菌谱与氨基糖苷类抗生素妥布霉素和庆大霉素相似。 它目前被批准作为各种严重感染的胃肠外治疗。静脉注射氨曲南已被证明是安全和有效的治疗下呼吸道感染的儿童CF。 这项III期、开放标签研究将入组已参加CP-AI-005或CP-AI-007研究的患者。这项试验正在研究氨曲南赖氨酸盐的多个疗程。每例受试者将接受至少2个周期的药物治疗，每个周期28天给药，28天停药。可选的第三个周期将由主要研究者决定

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. This phase 3, open-label study will enroll patients who have already participated in either the CP-AI-005 or CP-AI-007 studies. This trial is looking at multiple courses of Aztreonam Lysinate. Each participant will be on drug for at least 2 cycles of 28 days on and 28 days off. An optional third cycle will be up to the Principle Investigator