1 Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, Washington; and.
2 Core for Biomedical Statistics, Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington.
Ann Am Thorac Soc. 2018 Jun;15(6):702-709. doi: 10.1513/AnnalsATS.201801-012OC.
Azithromycin has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis. Concerns remain, however, regarding the potential emergence of treatment-related respiratory pathogens.
To determine whether chronic azithromycin use (defined as three-times weekly administration) is associated with increased rates of detection of eight specific respiratory pathogens.
We performed a new-user, propensity score-matched retrospective cohort study utilizing data from the Cystic Fibrosis Foundation Patient Registry. Incident azithromycin users were propensity score matched 1:1 with contemporaneous nonusers. Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate the association between chronic azithromycin use and incident respiratory pathogen detection. Analyses were performed separately for each pathogen, limited to patients among whom that pathogen had not been isolated in the 2 years before cohort entry.
After propensity score matching, the mean age of the cohorts was approximately 12 years. Chronic azithromycin users had a significantly lower risk of detection of new methicillin-resistant Staphylococcus aureus, nontuberculous mycobacteria, and Burkholderia cepacia complex compared with nonusers. The risk of acquiring the remaining five pathogens was not significantly different between users and nonusers.
Using an innovative new-user, propensity score-matched study design to minimize indication and selection biases, we found in a predominantly pediatric cohort that chronic azithromycin users had a lower risk of acquiring several cystic fibrosis-related respiratory pathogens. These results may ease concerns that chronic azithromycin exposure increases the risk of acquiring new respiratory pathogens among pediatric patients with cystic fibrosis.
阿奇霉素已被证明可改善囊性纤维化患者的肺功能并减少肺部恶化的次数。然而，人们仍然担心潜在的治疗相关呼吸道病原体的出现。
确定慢性阿奇霉素使用（定义为每周三次给药）是否与八种特定呼吸道病原体的检测率增加有关。
我们使用囊性纤维化基金会患者登记处的数据进行了一项新用户，倾向评分匹配的回顾性队列研究。将阿奇霉素的新使用者与同期非使用者进行倾向评分匹配 1:1。使用 Kaplan-Meier 曲线和 Cox 比例风险回归来评估慢性阿奇霉素使用与新呼吸道病原体检测之间的关联。对每种病原体分别进行分析，仅限于在队列入组前 2 年内未分离出该病原体的患者。
在进行倾向评分匹配后，队列的平均年龄约为 12 岁。与非使用者相比，慢性阿奇霉素使用者检测到新耐甲氧西林金黄色葡萄球菌、非结核分枝杆菌和洋葱伯克霍尔德菌复合菌的风险显著降低。使用者和非使用者之间获得其余五种病原体的风险无显着差异。
使用创新的新用户，倾向评分匹配的研究设计，最大程度地减少了指示和选择偏差，我们在主要是儿科的队列中发现，慢性阿奇霉素使用者获得几种囊性纤维化相关呼吸道病原体的风险较低。这些结果可能减轻了慢性阿奇霉素暴露会增加囊性纤维化儿科患者获得新呼吸道病原体的风险的担忧。
