Cystic fibrosis results from alterations in the CFTR protein, which regulates anion transport and mucociliary clearance in the airways. The absence or dysfunction of this protein leads to the accumulation of thickened mucus, providing a favorable environment for a wide range of bacterial and fungal infections. Lung disease develops within the first months of life and disrupts the immune system, establishing a vicious cycle of infection and inflammation that damages the respiratory epithelium. Among infectious agents, Pseudomonas aeruginosa remains the most frequently isolated pathogen in affected adults. Once acquired, this bacterium can become impossible to eradicate, leading to chronic colonization associated with deterioration of lung function. While several clinical and genetic factors predisposing to early infection have already been described, the role of prior infections by other pathogens remained unknown in children.
To address this gap, the authors followed 1,231 French patients under 18 years of age. Using the Kaplan-Meier method, they estimated the cumulative incidences of initial acquisition and chronic colonization for several microorganisms: methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, Achromobacter xylosoxidans, and Aspergillus species. Cox regression models were then used to analyze these prior infections as risk factors for the initial acquisition and chronic colonization by P. aeruginosa.
The results show that by the age of two, 65.5% of children had already experienced at least one initial bacterial or fungal acquisition, and 27.9% at least one chronic colonization. The median age of initial acquisition of P. aeruginosa was 5.1 years, with chronic colonization present in one quarter of patients by 14.7 years. MSSA was acquired by half of the children by 2.1 years, with progression to chronic colonization by 8.4 years in half of them. One quarter of patients were infected by S. maltophilia and by Aspergillus spp. at 7.9 and 9.7 years, respectively. The risk of acquisition and chronic colonization by P. aeruginosa increased with the initial acquisition of all other species, with hazard ratios reaching 2.19 (95% confidence interval: 1.18-4.07). This risk also increased with the number of prior acquisitions (hazard ratio of 1.89; 95% CI: 1.57-2.28), corresponding to a 16% increase per additional pathogen, a trend also observed for chronic colonization.
This work establishes that the airway microbial community can modulate the occurrence of P. aeruginosa. At the dawn of targeted therapies, it paves the way for characterizing future trends and developments in these infections.