Pathogen acquisition in patients with cystic fibrosis receiving ivacaftor or lumacaftor/ivacaftor

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.

High Prevalence of Staphylococcus aureus Enterotoxin Gene Cluster Superantigens in Cystic Fibrosis Clinical Isolates

“…Each isolate was grown on TSA containing either erythromycin, tetracycline, or chloramphenicol. Chronic azithromycin is routinely prescribed at the University of Iowa CF center [8]. The vast majority of isolates from the University of Iowa (75/77) exhibited erythromycin resistance, but tetracycline resistance was less common (12/77).…”

“…Unlike P. aeruginosa, which has multiple effective treatments to eradicate early infections and control chronic infections [3][4][5], S. aureus infections can be difficult to control with antibiotics [6]. CFTR modulator drugs may help prevent incident infections with S. aureus, but they are unlikely to eliminate chronic S. aureus infections [7,8]. Understanding how S. aureus infects and persists in the CF airway is critically important, as these infections may increase the risk of subsequent disease progression [9,10].…”

(R)-Roscovitine and CFTR modulators enhance killing of multi-drug resistant Burkholderia cenocepacia by cystic fibrosis macrophages

“…While new medications such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators are improving outcomes in CF, their high cost 3 , 4 prohibits widespread use in many countries and in those without (sufficient) insurance. Further, although infections are reduced on CFTR modulator treatment 5 , 6 , chronic infection remains a consistent feature 7 , indicating a continued need for novel approaches to the treatment of bacterial infections in CF.…”

Cystic fibrosis year in review 2019: Section 1 CFTR modulators

“…The decreased prevalence of PA infection was independent of reduced sputum sampling 19 . Similarly, in a single‐center comparison of a 3‐year period before and after ivacaftor approval, a significant delay in time to new acquisition of PA was demonstrated 20 …”