Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
Department of Pharmacy Practice and Science, University of Iowa College of Pharmacy, Iowa City, Iowa.
Pediatr Pulmonol. 2019 Aug;54(8):1200-1208. doi: 10.1002/ppul.24341. Epub 2019 Apr 22.
The cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor and lumacaftor/ivacaftor improve the status of existing infections in patients with cystic fibrosis (CF). It is unknown how well these drugs protect patients against incident infections. We hypothesized that CFTR modulator treatment would decrease new infections with Pseudomonas aeruginosa or Staphylococcus aureus.
We retrospectively studied a single-center cohort of patients with CF during two time periods (2008-2011, Era 1) and (2012-2015, Era 2) based on the January 2012 approval of ivacaftor. Using Kaplan-Meier analysis, we compared the time to any new infection with P. aeruginosa, methicillin-resistant S. aureus (MRSA), or methicillin-sensitive S. aureus (MSSA) that was absent during a 2-year baseline. We stratified the analysis based on whether patients received ivacaftor or lumacaftor/ivacaftor during Era 2. We used the log-rank test and considered P < 0.05 statistically significant.
For patients receiving ivacaftor or lumacaftor/ivacaftor in Era 2, there was a statistically significant delay in the time to new bacterial acquisition in Era 2 vs. Era 1 ( P = 0.008). For patients who did not receive CFTR modulators, there was a trend toward slower acquisition of new bacterial infections in Era 2 compared to Era 1, but this was not statistically significant ( P = 0.10).
Patients receiving ivacaftor or lumacaftor/ivacaftor for CF had significantly delayed acquisition of P. aeruginosa and S. aureus after these drugs were released. This method for analyzing incident infections may be useful for future studies of CFTR modulators and bacterial acquisition in CF registry cohorts.
囊性纤维化跨膜电导调节因子（CFTR）调节剂依伐卡托和拉那卡普特/依伐卡托改善了囊性纤维化（CF）患者现有感染的状况。目前尚不清楚这些药物能在多大程度上保护患者免受新的感染。我们假设 CFTR 调节剂治疗会减少铜绿假单胞菌或金黄色葡萄球菌的新发感染。
我们根据依伐卡托于 2012 年 1 月获得批准，回顾性地研究了两个时期（2008-2011 年，Era1）和（2012-2015 年，Era2）的单中心 CF 患者队列。使用 Kaplan-Meier 分析，我们比较了在 2 年基线期无任何新的铜绿假单胞菌、耐甲氧西林金黄色葡萄球菌（MRSA）或甲氧西林敏感金黄色葡萄球菌（MSSA）感染的时间。我们根据 Era2 期间患者是否接受依伐卡托或拉那卡普特/依伐卡托进行了分层分析。我们使用对数秩检验，认为 P<0.05 具有统计学意义。
在 Era2 期间接受依伐卡托或拉那卡普特/依伐卡托治疗的患者，与 Era1 相比，在 Era2 期间新细菌获得的时间有统计学显著延迟（P=0.008）。对于未接受 CFTR 调节剂治疗的患者，与 Era1 相比，在 Era2 期间新细菌感染的获得速度有变慢的趋势，但无统计学意义（P=0.10）。
接受依伐卡托或拉那卡普特/依伐卡托治疗的 CF 患者在这些药物上市后，铜绿假单胞菌和金黄色葡萄球菌的获得明显延迟。这种分析新感染的方法可能对 CFTR 调节剂和 CF 登记队列中细菌获得的未来研究有用。
