Impact of Antibiotics on the Lung Microbiome and Lung Function in Children with Cystic Fibrosis One Year after Hospitalization for an Initial Pulmonary Exacerbation

Abstract Background Cystic fibrosis (CF) is characterized by recurrent pulmonary exacerbations (PEx) and lung function decline. PEx are frequently treated with antibiotics. However, little is known about the cumulative effects of antibiotics on the airway microbiome of persons with CF over time. The purpose of this study was to evaluate changes in the microbiome and lung function in persons with CF over one-year following an initial study pulmonary exacerbation (iPEx). Methods Twenty children with CF ≤18 years of age were enrolled in the study which occurred prior to the routine administration of highly effective modulator therapy. Respiratory samples and spirometry were obtained at a minimum of quarterly visits and up to 1-year after an iPEx. Metagenomic sequencing was performed, and bacterial taxa were assigned using MetaPhlAn 2.0. Paired t test, ANOVA, and GLS regression were used to compare outcome variables. Results The mean (±SD) age of study participants at the time of the iPEx was 10.6 years. There was 3 ± 1.6 PEx treated with antibiotics per person with CF during the study period. Bacterial richness was similar at 1 year compared to iPEx (40.3 vs 39.3, p = 0.852), whereas the mean Shannon diversity index was significantly higher at one year (2.84 vs 1.62, p < 0.001). The number of PEx treated with IV or oral antibiotics over the year was not associated with changes in microbial diversity but was associated with changes in ppFVC (p < 0.001). Conclusions In our one-year prospective evaluation of children with CF hospitalized for IV antibiotic treatment of an initial PEx we found microbial diversity increased despite decreases in lung function associated with repeated PEx events requiring antibiotic therapy.