ANTIMICROBIAL THERAPY FOR NEW ONSET PSEUDOMONAS AERUGINOSA AIRWAY INFECTION

新发铜绿假单胞菌气道感染的抗菌治疗

基本信息

批准号：
7604858
负责人：
RICHARD C AHRENS
金额：
$ 0.1万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2007-09-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7604858
关键词：
Adolescent Adult Affect Age Age-Years Alginates Algorithms Antibiotic Resistance Antibiotic Therapy Bacterial Infections Breathing Child Chronic Clinical Computer Retrieval of Information on Scientific Projects Database Cystic Fibrosis Funding Grant Infant Infection Inflammatory Response Institution Lower respiratory tract structure Lung diseases Microbial Biofilms Morbidity - disease rate Obstructive Lung Diseases Oral Organism Oropharyngeal Outcome Participant Placebos Prevalence Pseudomonas aeruginosa Randomized Randomized Clinical Trials Rate Reporting Research Research Personnel Resources Respiratory System Safety Sampling Solutions Source Sputum Symptoms Time Tobramycin United States National Institutes of Health Variant Week airway inflammation antimicrobial children with cystic fibrosis cystic fibrosis patients day in vivo mortality pulmonary function respiratory

项目摘要

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.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它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的进行性阻塞性肺病。细菌感染和严重的中性粒细胞性气道炎症的开始时间比以前理解的要早得多，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，据报告，高达 20-30% 的婴儿、30-40% 的 2-10 岁儿童、约 60% 的青少年和约 80% 的成人呼吸道培养呈阳性与CF。慢性 Pa 支气管内感染的特征是高浓度的产生藻酸盐的粘液 Pa 变体，这些变体可能形成生物膜，使生物体对体内抗生素具有高度耐药性。一旦形成，慢性支气管内感染几乎不可能根除。 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死亡率更高。早年获得 Pa 也会对肺部疾病和生存产生不利影响。这项多中心、随机临床试验正在评估 CF 幼儿新发 Pa 阳性口咽、痰或下呼吸道培养物阳性时抗菌药物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接受两种早期抗假单胞菌治疗方案中的一种。无论随机分配如何，所有参与者都将接受初始疗程的抗假单胞菌抗生素治疗，包括 28 天的吸入妥布霉素溶液 (TSI) 和 14 天的口服环丙沙星/安慰剂疗程。如果第一个抗假单胞菌周期三周后呼吸道样本仍呈 Pa 阳性，参与者将接受额外的 28 天 TSI 疗程。