title: Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor.
abstract: BACKGROUND
  Ivacaftor improves outcomes in cystic fibrosis (CF) patients with the G551D mutation; however, effects on respiratory microbiology are largely unknown. This study examines changes in CF respiratory pathogens with ivacaftor and correlates them with baseline characteristics and clinical response.
  
  
  METHODS
  The G551D Observational Study enrolled a longitudinal observational cohort of US patients with CF aged 6 years and older with at least 1 copy of the G551D mutation. Results were linked with retrospective and prospective culture data in the US Cystic Fibrosis Foundation's National Patient Registry. Pseudomonas aeruginosa infection category in the year before and year after ivacaftor was compared and correlated with clinical findings.
  
  
  RESULTS
  Among 151 participants prescribed ivacaftor, 29% (26/89) who were culture positive for P. aeruginosa the year prior to ivacaftor use were culture negative the year following treatment; 88% (52/59) of those P. aeruginosa free remained uninfected. The odds of P. aeruginosa positivity in the year after ivacaftor compared with the year prior were reduced by 35% (odds ratio [OR], 0.65; P < .001). Ivacaftor was also associated with reduced odds of mucoid P. aeruginosa (OR, 0.77; P = .013) and Aspergillus (OR, 0.47; P = .039), but not Staphylococcus aureus or other common CF pathogens. Patients with intermittent culture positivity and higher forced expiratory volume in 1 second (FEV1) were most likely to turn culture negative. Reduction in P. aeruginosa was not associated with change in FEV1, body mass index, or hospitalizations.
  
  
  CONCLUSIONS
  Pseudomonas aeruginosa culture positivity was significantly reduced following ivacaftor treatment. Efficacious CFTR modulation may contribute to lower frequency of culture positivity for P. aeruginosa and other respiratory pathogens, particularly in patients with less established disease.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Coordinating Center.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Coordinating Center.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Center for CF Microbiology, Cystic Fibrosis Foundation Therapeutics Development Network, Seattle Children's Research Institute, Washington.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.affiliation: Coordinating Center.
authors.forename: Umer
authors.initials: U
authors.lastname: Khan
authors.affiliation: Coordinating Center.
authors.forename: Arthur
authors.initials: A
authors.lastname: Baines
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle Coordinating Center.
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.affiliation: Department of Medicine, University of Alabama at Birmingham.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000627:Aminophenols / Q000627:therapeutic use*; D001230:Aspergillus / Q000302:isolation & purification; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D020536:Enzyme Activators / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D015995:Prevalence; D011552:Pseudomonas Infections / Q000453:epidemiology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D015363:Quinolones / Q000627:therapeutic use*; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000627:Aminophenols; D020536:Enzyme Activators; D050505:Mutant Proteins; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR modulator; P. aeruginosa; cystic fibrosis; ivacaftor