Bacterial and fungal infections may increase risk of lung infections due to P. aeruginosa in children with CF

Amongst all infectious agents, Pseudomonas aeruginosa (Pa) remains the most frequently isolated pathogen in the airways of adults with Cystic fibrosis (CF) caused by variants encoding the CF transmembrane conductance regulator (CFTR) protein, which is crucial in regulating anion transport and mucociliary clearance in the airways.

Several clinical and genetic factors predispose to early Pa infections. However, the role of earlier infections with other pathogens on the risk of Pa infection in paediatric detrimental to people with cystic fibrosis (pwCF) remains unknown.

A new study in Journal of Cystic Fibrosis reveals that the bacterial and fungal infections increased the risk of lung infections caused by P. aeruginosa. This increase in risk was not due to a specific pathogen and was of a similar magnitude for all the studied typical CF pathogens.

Researchers used Kaplan–Meier method, they computed the cumulative incidences of bacterial and fungal initial acquisition (IA) and chronic colonisation (CC) in 1,231 French pwCF under 18 years of age for methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, Achromobacter xylosoxidans, and Aspergillus species. Previous infections were analysed as Pa-IA and Pa-CC risk factors using Cox regression models.

The key findings of the study are

• By 2 years of age, 65.5% pwCF had experienced at least one bacterial or fungal IA, and 27.9% had experienced at least one CC.

• The median age of Pa-IA was 5.1 years, and Pa-CC was present in 25% pwCF by 14.7 years. While 50% acquired MSSA at 2.1 years, 50% progressed to chronic MSSA colonisation at 8.4 years.

• At 7.9 and 9.7 years, 25% pwCF were infected by S. maltophilia and Aspergillus spp., respectively.

• The risk of Pa-IA and Pa-CC increased with IAs of all other species, with hazard ratios (HR) up to 2.19 (95% Confidence interval (CI) 1.18–4.07).

• The risk of Pa-IA increased with the number of previous bacterial/fungal IAs (HR=1.89, 95% CI 1.57–2.28), with a 16% increase per additional pathogen; same trend was noted for Pa-CC.

Researchers concluded that “This study establishes that the microbial community in CF airways can modulate Pa occurrence. At the dawn of targeted therapies, it paves the way for characterizing future trends and evolution of infections.”

Reference: Julie Mésinèle, Manon Ruffin, Loïc Guillot, Pierre-Yves Boëlle, Harriet Corvol,; Airway infections as a risk factor for Pseudomonas aeruginosa acquisition and chronic colonisation in children with cystic fibrosis, Journal of Cystic Fibrosis,2023; DOI: https://doi.org/10.1016/j.jcf.2023.06.007.