Effect of Elexacaftor/Tezacaftor/Ivacaftor on Pseudomonas aeruginosa Acquisition and Chronic Infection at a Single Pediatric Cystic Fibrosis Care Center

Abstract

OBJECTIVES As cystic fibrosis (CF) lung disease progresses, the airways become infected with opportunistic pathogens, such as Pseudomonas aeruginosa (PA). In October 2019, the US Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective modulator therapy (HEMT), for individuals 12 years and older with 1 copy of the F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation. ETI increases the amount of and function of CFTR in the respiratory epithelium, improving mucociliary clearance and reducing static airway mucus, a major trigger for chronic infection and inflammation. METHODS A retrospective analysis of inhaled tobramycin (iTOB) prescriptions between January 1, 2016, and December 31, 2021, was performed. This captured data before and after ETI approval at Children’s Mercy Kansas City (CMKC). The number of individuals with new PA acquisition and individuals considered ­chronically infected was analyzed. RESULTS The number of eradication prescriptions declined in 2020 and 2021, with 15 (7%) and 12 (5%) ­individuals prescribed therapy for those years, respectively. A similar pattern was observed for ­prescriptions for chronic infection. A reduction was seen in 2020 and 2021, with 28 (13%) and 20 (9%) individuals ­prescribed therapy for the respective years. CONCLUSIONS The CMKC experienced a decrease in the number of courses of iTOB prescribed during the last 6 years. The reasons for this are likely multifactorial and may include the implementation of standardized PA surveillance and eradication protocols, the effect of HEMT on mucociliary clearance and airway microbiology, and the poorly understood effects of the SARS-CoV-2 pandemic on the epidemiology of respiratory infections.