Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis

Abstract

Background: High bacterial burden in lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases and observational studies have shown a positive effect of azithromycin on mortality and hospitalization rate in IPF. However, the effect of AZT on lung microbiota in IPF remain unknown.Methods: We sought to determine the impact of a three-month course of azithromycin on lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomized controlled cross-over trial of a thrice-weekly 500 mg oral azithromycin. 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARG) were assessed using real-time qPCR.Results: Azithromycin significantly decreased community diversity with a stronger and more persistent effect in lower airways. During treatment, turnover of airway microbiota decreased in upper and lower airways, resulting in greater similarity between microbiota of the two sites persisting one month after macrolide cessation. Patients with increased expression of ARG had a lower bacterial load and an enrichment of the genus Streptococcus. In contrast, patients without increased in ARG expression had a higher bacterial load and an enrichment in Prevotella.Conclusions: We observed that AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.