Pathogen acquisition in patients with cystic fibrosis receiving ivacaftor or lumacaftor/ivacaftor.
Adolescent
Adult
Aminophenols
/ therapeutic use
Aminopyridines
/ therapeutic use
Benzodioxoles
/ therapeutic use
Child
Child, Preschool
Cystic Fibrosis
/ drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator
Drug Combinations
Female
Humans
Male
Pseudomonas Infections
/ prevention & control
Pseudomonas aeruginosa
Quinolones
/ therapeutic use
Retrospective Studies
Staphylococcal Infections
/ prevention & control
Staphylococcus aureus
Young Adult
CFTR
Pseudomonas aeruginosa
Staphylococcus aureus
cystic fibrosis
ivacaftor
lumacaftor
Journal
Pediatric pulmonology
ISSN: 1099-0496
Titre abrégé: Pediatr Pulmonol
Pays: United States
ID NLM: 8510590
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
10
01
2019
revised:
14
03
2019
accepted:
05
04
2019
pubmed:
24
4
2019
medline:
24
3
2020
entrez:
24
4
2019
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31012285
doi: 10.1002/ppul.24341
pmc: PMC6641998
mid: NIHMS1025714
doi:
Substances chimiques
Aminophenols
0
Aminopyridines
0
Benzodioxoles
0
CFTR protein, human
0
Drug Combinations
0
Quinolones
0
lumacaftor, ivacaftor drug combination
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1200-1208Subventions
Organisme : NICHD NIH HHS
ID : K12 HD027748-23
Pays : United States
Organisme : NHLBI NIH HHS
ID : L40 HL134155
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD027748
Pays : United States
Organisme : NIH HHS
ID : NIH K08 HL136927
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK054759
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL136927
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL136927
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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