ANTIMICROBIAL THERAPY FOR NEW ONSET PSEUDOMONAS AERUGINOSA AIRWAY INFECTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。囊性纤维化（CF）患者发病和死亡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。细菌感染和稳健的中性粒细胞气道炎症开始的时间远早于以前的认识，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、约60%的青少年和约80%的CF成人的呼吸道培养呈阳性。慢性Pa支气管内感染的特征是高浓度的产生海藻酸盐的粘液样Pa变异体，这些变异体可能形成生物膜，使生物体在体内对抗生素具有高度耐药性。慢性支气管内Pa感染一旦建立，几乎不可能根除。Pa感染显然与较差的临床结果相关，包括肺功能更快下降和更高的死亡率。过早获得Pa也会对肺部疾病和生存产生不利影响。这项多中心随机临床试验旨在评估CF患儿新发Pa阳性口咽、痰或下呼吸道培养时抗菌治疗的临床和微生物学疗效和安全性。受试者将被随机分配到两种早期抗假单胞菌治疗算法中的一种。所有参与者将接受抗假单胞菌抗生素治疗的初始疗程，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，无论随机分配如何。如果在第一个抗假单胞菌周期的三周后，呼吸培养样本仍呈Pa阳性，参与者将接受额外的28天TSI疗程。

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.