Related Experiment Video
Updated: Sep 23, 2026

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Changes in Inhaled Antibiotic Associated lung function outcomes in the CFTR-Modulator Era
Marianne S Muhlebach1, Jane She2, John J LiPuma3
1Dept of Pediatrics and Marsico Lung Institute, University of North Carolina at Chapel Hill, USA.
Background:
Chronic inhaled antibiotics are recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (Pa). Yet, chronic antibiotics may increase risk for other infections and benefits may have changed as outcomes of pwCF improved.
Research Question:
Does the risk of infections associated with inhaled antibiotic prescriptions and the treatment benefit on lung function differ by Pa infection status and has the antibiotic-associated treatment effect changed since introduction of CFTR-modulators.
Study Design And Methods:
US CF-Foundation Patient Registry data were analysed for the years 2011-2019. Pa infection status was defined per Leeds criteria. Analyses included inverse probability treatment weighting. Survival modeling compared differences in incidence of Aspergillus and Gram-negatives between pwCF prescribed versus not prescribed antibiotics-within each Pa infection cohort. Differences in lung function associated with inhaled antibiotics were modeled using generalized estimating equations, with testing whether the mean effect of antibiotics differed across CFTR-modulator eras (ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor).
Results:
From 2011 to 2019 the number of pwCF analysed increased from 12,000 to 16,041, with decreasing prevalence in chronic Pa, increasing age and better lung function. Risk of Aspergillus infections was higher in antibiotic prescribed vs. non-prescribed pwCF: HR 1.33 (CI95% 1.26, 1.41) and was significantly higher in Pa negative compared to Pa chronic pwCF. Similarly, inhaled antibiotics were associated with increased risk of Stenotrophomonas maltophilia and Achromobacter: HR 1.21, (CI95% 1.14, 1.29) and 1.26 (CI95% 1.14, 1.39), respectively. Inhaled antibiotics were associated with higher lung function in chronic Pa but lower lung function in Pa negative pwCF. The antibiotic-associated treatment effect on lung function decreased over the three eras of CFTR-modulators.
Interpretation:
The risk of treatment emergent infections was highest in Pa negative pwCF who conversely did not have antibiotic-associated benefit on lung function. For pwCF with chronic Pa the antibiotic-associated benefit decreased as CFTR-modulator use increased.
Related Concept Videos
Cystic Fibrosis: Management
Sinus disease and chronic sinusitis...
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
COPD: Management Using Bronchodilators and Corticosteroids
Inhaled Medications
Chronic Obstructive Pulmonary Disease-I: Introduction

