Treatment of Persistent MRSA Infection in Cystic Fibrosis Patients

囊性纤维化患者持续性 MRSA 感染的治疗

• 批准号: 8981612
• 负责人: Rebecca Hope Dezube
• 金额: $ 7.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981612
• 关键词: Age; Aminoglycosides; Antibiotic Resistance; Antibiotics; Breathing; Bronchial Spasm; Case Study; Caucasians; Cause of Death; Chemistry; Chronic; Clinical; Controlled Clinical Trials; Cystic Fibrosis; Data; Decontamination; Disease; Dose; Double-Blind Method; Enrollment; Folic Acid; Goals; Guidelines; Hematology; Hereditary Disease; Hospitals; Individual; Infection; Intravenous; Lead; Lung; Measures; Medical; Methods; Oral; Outcome; Outcome Study; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Prevalence; Publishing; Randomized; Randomized Controlled Trials; Regimen; Resistance; Resistance profile; Respiratory Failure; Respiratory System; Respiratory physiology; Respiratory tract structure; Role; Safety; Scientist; Series; Serious Adverse Event; Serum; Site; Spirometry; Sputum; Staphylococcus aureus; Sulfamethoxazole; Taste Perception; Time; Training; Treatment Protocols; Trimethoprim; Trimethoprim-Sulfamethoxazole; University Hospitals; Vancomycin; Variant; Visit; Withholding Treatment; career development; clinical research site; cystic fibrosis patients; double-blind placebo controlled trial; methicillin resistant Staphylococcus aureus; mortality; pathogen; public health relevance; screening

 DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in Caucasians. Despite significant advances in medical therapy which have led to an increase in the median predicted age of survival from one year in 1950 to 40.7 years in 2013, the leading cause of mortality in CF patients remains respiratory failure due to pulmonary infection. Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important infectious pathogen in the CF population. The prevalence of MRSA pulmonary infection in the CF population has dramatically increased over the last twenty years, from less than 5% of patients in 1996 to 24.6% of patients in 2013. A series of studies completed by our group and others has shown that chronic and persistent MRSA infection is strongly associated with a more rapid decline in lung function and decreased survival in CF patients. However, there are no guidelines regarding treatment of MRSA infection in this population, nor have there been any completed randomized-control trials that examine treatment of persistent MRSA in CF patients. This study aims to investigate the safety and efficacy of inhaled vancomycin in treating persistent MRSA infection in CF patients. Inhaled antibiotics are a cornerstone of CF treatment for other pulmonary infections as this mode of administration allows the drug to be delivered directly to the site of infection. Intravenous vancomycin is one of the antibiotics most commonly used to treat MRSA infection. There have been multiple case reports suggesting that inhaled vancomycin is an effective method of treating pulmonary MRSA infection in both CF and non-CF populations, and that inhaled vancomycin is safe and well-tolerated. We have therefore initiated a randomized, double-blind, placebo-controlled trial studying inhaled vancomycin and its effects on the eradication of MRSA in patients with CF and persistent MRSA infection. We aim to enroll 40 patients at two clinical sites (Johns Hopkins Hospital and Case Western University Hospital) half of whom will receive our study drug and half who will receive taste-matched placebo for a 28-day time period. In addition to investigating the use of inhaled vancomycin in treating persistent MRSA infection in patients with CF, implementation of this proposal will provide training for the candidate that will be instrumental toward her career development and goal of becoming a clinician-scientist studying infection in cystic fibrosis.

 描述(申请人提供)：囊性纤维化(CF)是高加索人最常见的致死性常染色体隐性遗传病。尽管医学治疗取得了重大进展，导致预测存活年龄的中位数从1950年的一岁提高到2013年的40.7岁，但慢性阻塞性肺疾病患者死亡的主要原因仍然是肺部感染导致的呼吸衰竭。耐甲氧西林金黄色葡萄球菌(MRSA)已成为CF人群中的一种重要感染性病原体。在过去的20年里，慢性阻塞性肺疾病患者中MRSA肺部感染的患病率急剧上升，从1996年的不到5%上升到2013年的24.6%。我们小组和其他人完成的一系列研究表明，慢性和持续的MRSA感染与CF患者肺功能更快的下降和生存率的下降密切相关。然而，目前还没有关于这一人群中MRSA感染的治疗指南，也没有任何完整的随机对照试验来检查CF患者持续MRSA的治疗。本研究旨在观察雾化吸入万古霉素的安全性和有效性。 慢性萎缩性胃炎患者持续耐甲氧西林金黄色葡萄球菌感染吸入抗生素是CF治疗其他肺部感染的基石，因为这种给药模式允许药物直接输送到感染部位。静脉注射万古霉素是治疗MRSA感染最常用的抗生素之一。已有多个病例报告表明，吸入万古霉素是治疗慢性阻塞性肺疾病和非慢性阻塞性肺疾病患者肺部MRSA感染的有效方法，且万古霉素吸入治疗安全且耐受性良好。因此，我们启动了一项随机、双盲、安慰剂对照试验，研究吸入万古霉素及其对CF和持续性MRSA感染患者MRSA根除的影响。我们的目标是在两个临床地点(约翰·霍普金斯医院和凯斯西部大学医院)招募40名患者，其中一半将接受我们的研究药物，另一半将接受为期28天的味觉匹配安慰剂治疗。除了调查吸入性万古霉素在治疗CF患者持续MRSA感染方面的使用外，这项提议的实施还将为候选人提供培训，这将有助于她的职业发展和成为研究囊性纤维化感染的临床医生和科学家的目标。