ANTIMICROBIAL THERAPY FOR NEW ONSET PSEUDOMONAS AERUGINOSA AIRWAY INFECTION

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。囊性纤维化患者的发病率和死亡率的主要原因是进行性阻塞性肺疾病与慢性铜绿假单胞菌(PA)支气管内感染和相关的强烈中性粒细胞炎症反应相关。细菌感染和强中性粒细胞呼吸道炎症的开始时间比以前了解的要早得多，通常在症状出现之前。PA感染的患病率随着年龄的增长而增加，据报道，高达20%-30%的婴儿、30%-40%的2-10岁儿童、大约60%的青少年和大约80%的成人CF患者的呼吸道培养呈阳性。慢性巴氏杆菌支气管内感染的特征是高浓度的产生藻酸盐的粘液性巴氏杆菌变异体，这些变异体可能形成生物被膜，使生物对体内的抗生素产生高度耐药性。一旦确诊，慢性肺炎杆菌呼吸道感染实际上是不可能根除的。PA感染明显与较差的临床结局相关，包括肺功能更快的下降和更高的死亡率。早年的PA获得性疾病也会对肺部疾病和存活率产生不利影响。这项多中心随机临床试验正在评估在新发的PA阳性口咽、痰或下呼吸道培养阳性的儿童CF患者中使用抗菌药物治疗的临床和微生物疗效和安全性。受试者将被随机接受两种早期抗假单胞菌治疗算法之一。无论随机分配，所有参与者都将接受最初的抗假单胞菌抗生素治疗，包括28天的妥布霉素吸入溶液(TSI)和14天的口服环丙沙星/安慰剂疗程。如果在第一个抗假单胞菌周期的三周后，呼吸刀样本仍为PA阳性，参与者将接受额外的28天疗程的TSI。

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. The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive lung disease associated with chronic Pseudomonas aeruginosa (Pa) endobronchial infection and the associated intense neutrophilic inflammatory response. Bacterial infection and robust neutrophilic airway inflammation begin far earlier than previously understood, often prior to the onset of symptoms. The prevalence of Pa infection increases with age, with positive respiratory tract cultures reported for up to 20-30% of infants, 30-40% of children 2-10 years of age, approximately 60% of adolescents, and approximately 80% of adults with CF. Chronic Pa endobronchial infection is characterized by high concentrations of alginate-producing mucoidy Pa variants that may form biofilms rendering the organisms highly resistant to antibiotics in vivo. Once established, chronic Pa endobroncial infection is virtually impossible to eradicate. Pa infection is clearly associatd with poorer clinical outcomes, including more rapid decline in pulmonary function and higher mortality rates. Early age of Pa acquisition also adversely affects pulmonary disease and survival. This multicenter, randomized clinical trial is assessing the clinical and microbiologic efficacy and safety of treatment with antimicrobial therapy at the time of new onset of Pa positive oropharyngeal, sputum or lower respiratory tract culture in young children with CF. Subjects will be randomized to one of two early anti-pseudomonal treatment algorithms. All participants will receive an initial course of anti-pseudomonal antibiotic therapy consisting of 28 days of tobramycin solution for inhalation (TSI) and a 14-day course of oral ciprofloxicin/placebo regardless of randomization assignment. If respiratory cutlures samples after three weeks of the first anti-pseudomonal cycle remain Pa positive, participants will receive an additional 28-day course of TSI.