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.

Keywords: CFTR modulator; P. aeruginosa; cystic fibrosis; ivacaftor.

Figure 1.

Prevalence of culture positivity for cystic fibrosis pathogens before (open triangle and square) and after (solid square) initiation of ivacaftor. Prevalence reported among those with at least 1 respiratory culture in each year: 93% 2 years prior, 98% year prior, and 90% year after. P value reported for test comparing prevalence of each organism in year after to year prior. Vertical lines are 95% confidence intervals of the prevalence. Abbreviations: Asperg., Aspergillus species; B.cep, B. cepacia complex; H.flu, H. influenzae; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; Pa, P. aeruginosa; S.malt, S. maltophilia.

Figure 2.

Change in Pseudomonas aeruginosa frequency from year before to after ivacaftor initiation, stratified by number of respiratory cultures per year. Reduction includes transition from persistent infection (>50%) to intermittent infection (1%–50%) or infection free (0%), and intermittent infection to infection free. Increase includes transition from infection free to intermittent infection or persistent infection, and intermittent infection to persistent infection.