Beck Michael R, Hornick Douglas B, Pena Tahuanty A, Singh Sachinkumar B, Wright Brittany A
University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Pediatr Pulmonol. 2023 May;58(5):1569-1573. doi: 10.1002/ppul.26362. Epub 2023 Mar 1.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have shown beneficial effects on both forced expiratory volume in 1 s (FEV ) and frequency of pulmonary exacerbations in people with cystic fibrosis (CF). These positive outcomes may be related to changes in bacterial colonization within the lungs. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the first triple therapy CFTR modulator approved for use in people with CF 6 years and older. This study aimed to determine the impact of ELX/TEZ/IVA on the isolation of Pseudomonas aeruginosa (Pa), methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA, respectively) in respiratory cultures.
A retrospective chart review of the electronic medical record at the University of Iowa was completed for individuals 12 years and older taking ELX/TEZ/IVA for at least 12 months. The primary outcome was determined by assessing bacterial cultures pre- and postinitiation of ELX/TEZ/IVA. Baseline demographic and clinical characteristics were summarized using mean and standard deviation for continuous outcomes and count and percentage for categorical outcomes. Culture positivity for Pa, MSSA, and MRSA was compared among enrolled subjects between pre- and posttriple combination therapy periods using an exact McNemar's test.
One hundred and twenty-four subjects prescribed ELX/TEZ/IVA for at least 12 months met the requirements for inclusion within our analysis. Culture positivity for Pa, MSSA, and MRSA was approximately 54%, 33%, and 31%, respectively, for the pre-ELX/TEZ/IVA period. Prevalence decreased to approximately 30%, 32%, and 24% (-24.2% [p < 0.0001], -0.7% [p = 1.00], and -6.5% [p = 0.0963], respectively) post-ELX/TEZ/IVA. The source of bacterial culture was predominantly sputum (70.2%) in the pre-ELX/TEZ/IVA group, whereas a throat source (66.1%) was more common post-ELX/TEZ/IVA.
ELX/TEZ/IVA treatment has an appreciable impact on the detection of common bacterial pathogens in CF respiratory cultures. While previous studies have found a similar effect with single and double CFTR modulator therapies, this is the first single-center study to show the impact of triple therapy, ELX/TEZ/IVA, on bacterial isolation from airway secretions.
囊性纤维化跨膜传导调节因子（CFTR）调节剂已显示出对囊性纤维化（CF）患者的1秒用力呼气量（FEV₁）和肺部恶化频率均有有益影响。这些积极结果可能与肺部细菌定植的变化有关。依列卡托/替扎卡托/依伐卡托（ELX/TEZ/IVA）是首个获批用于6岁及以上CF患者的三联疗法CFTR调节剂。本研究旨在确定ELX/TEZ/IVA对呼吸道培养物中铜绿假单胞菌（Pa）、耐甲氧西林金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌（分别为MRSA和MSSA）分离的影响。
对爱荷华大学12岁及以上服用ELX/TEZ/IVA至少12个月的个体的电子病历进行回顾性图表审查。主要结局通过评估ELX/TEZ/IVA开始前和开始后的细菌培养来确定。连续结局用均值和标准差总结，分类结局用计数和百分比总结基线人口统计学和临床特征。使用精确的McNemar检验比较三联联合治疗前和治疗后入组受试者中Pa、MSSA和MRSA的培养阳性率。
124名接受ELX/TEZ/IVA治疗至少12个月的受试者符合纳入我们分析的要求。在ELX/TEZ/IVA治疗前，Pa、MSSA和MRSA的培养阳性率分别约为54%、33%和31%。ELX/TEZ/IVA治疗后，患病率分别降至约30%、32%和24%（分别为-24.2% [p＜0.0001]、-0.7% [p = 1.00]和-6.5% [p = 0.0963]）。ELX/TEZ/IVA治疗前细菌培养的来源主要是痰液（70.2%），而ELX/TEZ/IVA治疗后咽喉来源（66.1%）更为常见。
ELX/TEZ/IVA治疗对CF呼吸道培养物中常见细菌病原体的检测有显著影响。虽然先前的研究发现单药和双药CFTR调节剂疗法有类似效果，但这是第一项显示三联疗法ELX/TEZ/IVA对气道分泌物细菌分离影响的单中心研究。
