Impact of Elexacaftor/Tezacaftor/Ivacaftor on Systemic Antibiotic Utilization in Pediatric Patients With Cystic Fibrosis

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recurrent respiratory infections are a common problem, and patients receive frequent antibiotics. Treatment of CF involves both symptomatic and underlying disease-targeting therapies. Elexacaftor/tezacaftor/ivacaftor (ETI), a disease-targeting therapy, combines two correctors and a potentiator to increase functioning of the CFTR channel. With better functioning channels, symptomatic improvement is expected in the form of decreased respiratory infections. OBJECTIVE: To evaluate the change in antibiotic use following the initiation of ETI therapy in pediatric patients. METHODS: This is a single-center, retrospective chart review conducted at Nationwide Children's Hospital (NCH) in Columbus, Ohio. Patients served as self-controls, compared before and after initiating ETI. The primary outcome was change in antibiotic days per patient-year. Secondary outcomes included change in use of specific antibiotics, enteral versus intravenous (IV) therapy, and different classes of antibiotics. The study was approved by the NCH institutional review board (IRB). RESULTS: The study included 139 patients aged 6-18 years. The median antibiotic days per patient-year was 17 days pre-ETI and 6 days post-ETI (p < 0.001). There was a significant decrease in antibiotic days per patient-year for subgroups of IV antibiotics, enteral antibiotics, IV vancomycin, linezolid and tedizolid, anti-methicillin-resistant Staphylococcus aureus (MRSA) tetracyclines, other anti-MRSA medications (clindamycin and trimethoprim/sulfamethoxazole), aminoglycosides, anti-Pseudomonas aeruginosa (Psae) beta-lactams, and fluoroquinolones. There was no significant difference for carbapenems or non-anti-Psae beta-lactams. CONCLUSION: ETI therapy was associated with decreased antibiotic days for many therapeutic classes of both enteral and IV antibiotics.