Jennings Mark T, Boyle Michael P, Weaver David, Callahan Karen A, Dasenbrook Elliott C
Johns Hopkins Medical Institutions, 1830 E, Monument Street, 5th floor, Baltimore, Maryland 21205, USA.
Trials. 2014 Jun 12;15:223. doi: 10.1186/1745-6215-15-223.
The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) respiratory infection in cystic fibrosis (CF) has increased dramatically over the last decade, and is now affecting approximately 25% of patients. Epidemiologic evidence suggests that persistent infection with MRSA results in an increased rate of decline in FEV1 and shortened survival. Currently, there are no conclusive studies demonstrating an effective and safe treatment protocol for persistent MRSA respiratory infection in CF.
METHODS/DESIGN: The primary objective of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation in combination with oral antibiotics in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. This is a two-center, randomized, double-blind, comparator-controlled, parallel-group study with 1:1 assignment to either vancomycin for inhalation (250 mg twice a day) or taste-matched placebo for 28 days in individuals with cystic fibrosis. In addition, both groups will receive oral rifampin, a second oral antibiotic - trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol determined - mupirocin intranasal cream, and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled: 20 will be randomized to vancomycin for inhalation and 20 to a taste-matched placebo. The primary outcome will be the presence of MRSA in sputum respiratory tract cultures 1 month after the conclusion of treatment. Secondary outcomes include the efficacy of the intervention on: FEV1% predicted, patient reported outcomes, pulmonary exacerbations, and MRSA colony-forming units found in respiratory tract sample culture.
Results of this study will provide guidance to clinicians regarding the safety and effectiveness of a targeted eradication strategy for persistent MRSA infection in CF.
This trial is registered at ClinicalTrials.gov (NCT01594827, received 05/07/2012) and is funded by the Cystic Fibrosis Foundation (Grants: PMEP10K1 and PMEP11K1).
在过去十年中，耐甲氧西林金黄色葡萄球菌（MRSA）呼吸道感染在囊性纤维化（CF）患者中的患病率急剧上升，目前约25%的患者受其影响。流行病学证据表明，MRSA持续感染会导致第一秒用力呼气容积（FEV1）下降速度加快和生存期缩短。目前，尚无确凿研究证明针对CF患者MRSA持续呼吸道感染的有效且安全的治疗方案。
方法/设计：本研究的主要目的是评估为期28天的吸入用万古霉素联合口服抗生素方案在清除CF合并MRSA持续感染个体呼吸道中MRSA方面的安全性和有效性。这是一项双中心、随机、双盲、对照比较、平行组研究，按1:1比例将囊性纤维化患者随机分配至吸入用万古霉素组（每日两次，每次250毫克）或口味匹配的安慰剂组，为期28天。此外，两组均将接受口服利福平、第二种口服抗生素（根据方案确定为甲氧苄啶/磺胺甲恶唑（TMP/SMX）或强力霉素）、鼻用莫匹罗星乳膏和洗必泰沐浴露。将招募40例呼吸道MRSA持续感染患者：20例随机分配至吸入用万古霉素组，20例分配至口味匹配的安慰剂组。主要结局为治疗结束1个月后痰液呼吸道培养物中是否存在MRSA。次要结局包括干预措施对以下方面的疗效：预测FEV1%、患者报告结局、肺部加重以及呼吸道样本培养中发现的MRSA菌落形成单位。
本研究结果将为临床医生提供关于CF患者MRSA持续感染靶向根除策略的安全性和有效性的指导。
本试验已在ClinicalTrials.gov注册（NCT01594827，于2012年7月5日获得），由囊性纤维化基金会资助（赠款：PMEP10K1和PMEP11K1）。
