Modulator therapy: rates and stages of respiratory bacteriome restoration in cystic fibrosis patients chronically infected with Pseudomonadota

BACKGROUND: Chronic lung infection caused by Pseudomonadota (PCH) in patients with cystic fibrosis (pwCF) is difficult to eradicate. CFTR modulators have a potential role in the prevention of airway infections, but their ability to eradicate chronic infection remains to be investigated. The aim of our study was to evaluate the impact of combination (antibacterial (AT) and modulator (MT)) therapy on the lung bacteriome composition (LBC) in the pwCF cohort. RESULTS: The bacteriomes of sputum samples longitudinally collected from 57 Russian adult pwCFs chronically infected with Pseudomonadota CF pathogens (PCH) were analyzed. MT tended to reduce the bacterial load. The LMC did not significantly change in PCH pwCFs that received MT for less than three years. Two-component MT resulted in a temporary decrease in the proportion of the CF pathogen only when combined with a course of AT. Three-component MT has been successful in inducing favorable bacteriome changes (in terms of the abundance and diversity of anaerobic taxa) over a period of more than 3 years but not for all cases of Burkholderiales infection. CONCLUSIONS: The respiratory system damaged by bronchiectasis is susceptible to new infections, so patient management requires constant monitoring of the LBC and replenishment of the therapeutic landscape with both new modulators and new antibacterial drugs.