One year of ETI reduces lung bacterial colonisation in adults with cystic fibrosis

The triple combination elexacaftor-tezacaftor-ivacaftor (ETI) has provided unprecedented clinical benefits for people with cystic fibrosis (pwCF) and drastically transformed the outcome of this disease. We aimed to describe the evolution of lung bacterial colonization in 198 French adult pwCF taking into account the use of concomitantly respiratory treatment. We collected sputum cultures produced during the entire follow-up period starting 3 years before and ending 1 year after ETI initiation. All sputum cultures were centralized and analyzed at our bacteriological laboratory. Clinical data included pulmonary function, respiratory treatments, physiotherapy, number of IV antibiotics treatment, as well as inpatient stays. We observed a significant decrease in colonization prevalence by any CF pathogen after one year of treatment with ETI (p < 0.001). This decrease was confirmed for Pseudomonas aeruginosa, MRSA and MSSA, Stenotrophomonas maltophilia, Achromobacter spp. and nontuberculous mycobacteria (NTM). The maximal density of bacteria documented in sputum cultures decreased from 2.10⁷ CFU/ml to 1.10⁶ CFU/ml after one year of ETI. We also found a decrease in prevalence of Pseudomonas aeruginosa chronic colonization and in the density of Pseudomonas aeruginosa after one year of ETI. These results confirm the decrease in prevalence and bacterial density of lung colonisation for most of the CF pathogens, including Achromobacter spp, Stenotrophomonas maltophilia concomitantly to the clinical improvement. Further studies are needed to better understand the underlying mechanisms of these microbiological changes.