Impact of Elexacaftor/Tezacaftor/Ivacaftor on Microbiology and Antibiotic Utilization in People With Cystic Fibrosis

Background: Cystic fibrosis (CF) is a multisystem disease characterized by persistent lung infection. Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves respiratory-related quality of life and reduces rates of infection and antibiotic treatments. Reduced antibiotic use may alter bacterial drug resistance patterns. Methods: This was a single center, retrospective, observational study analyzing respiratory cultures obtained from people with CF (pwCF) before and after starting ETI therapy. Antibiotic courses and culture data, including susceptibilities, were obtained from the electronic medical record. Results: There were 312 pwCF on ETI included, with an average age at ETI initiation of 20.9 +/- 12.0 years and an average length of time on ETI 2.48 +/- 0.69 years. Compared to the pre-ETI period, pwCF post-ETI had reductions in the number of antibiotic courses per year (2.5 to 0.7, p < 0.001), antibiotics utilized per course (1.4 to 1.0, p < 0.001), and percentage of courses including intravenous antibiotics (59% to 38%, p < 0.001). The fraction of pwCF with at least one culture positive for Pseudomonas aeruginosa, Burkholderia species, or Stenotrophomonas maltophilia decreased after ETI initiation, though changes were not significant for Staphylococcus aureus. Antibacterial resistance patterns were similar for most antibiotics in pre- and post-ETI periods, with P. aeruginosa exhibiting more resistance to fluoroquinolones post-ETI. Individuals with resistant organisms pre-ETI were less likely to clear the pathogen post-ETI. Conclusion: Treatment with ETI significantly decreased antibiotic utilization and the prevalence of gram-negative organisms. Although fewer antibiotics were used, antibiotic resistance remained unchanged or even increased post-ETI due largely to the greater persistence of resistant organisms.