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  • Title: Pathogen acquisition in patients with cystic fibrosis receiving ivacaftor or lumacaftor/ivacaftor.
    Author: Singh SB, McLearn-Montz AJ, Milavetz F, Gates LK, Fox C, Murry LT, Sabus A, Porterfield HS, Fischer AJ.
    Journal: Pediatr Pulmonol; 2019 Aug; 54(8):1200-1208. PubMed ID: 31012285.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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