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

Abstract

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.

Keywords: Haemophilus influenzae; Pseudomonas aeruginosa; Staphylococcus aureus; Cystic fibrosis; Elexacaftor-tezacaftor-ivacaftor; Nontuberculous mycobacteria.

Fig. 1

Evolution of clinical features. (A) evolution of lung function before and after ETI, ppFEV1%. (B) Evolution of respiratory symptoms, estimated by the frequency of weekly physiotherapy sessions and the number of PEx per patient per year. (C) Evolution of treatment load, focusing on pulmonary treatments: mucolytic agents, inhaled antibiotics, azithromycin. (D) Evolution of number of inpatients per year and length of stay hospitalisations stay.

Fig. 2

Mean density of CF pathogens in sputum cultures (CFU/ml) at a one-year interval from ETI introduction (Y-2: 2 years before ETI introduction, Y-1: 1 year before ETI introduction, Y0: at ETI introduction, Y + 1: the year following ETI introduction).

Fig. 3

Change of Pseudomonas aeruginosa colonisation status from Y0 (at ETI initiation) to Y + 1 (one year after ETI initiation). Colonisation was considered as chronic if more than half the sputum cultures were positive during the year; as intermittent if less than half the sputum cultures were positive during the year and patient was considered as free if previously colonised and no Pa was documented during the year. A minimum of 2 sputum cultures per year was required.