Abstract
Background High bacterial burden in lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) 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 remains unknown.
Methods We sought to determine the impact of a three-month course of AZT 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 AZT. 16S rRNA gene amplicon sequencing and quantitative polymerase chain reaction (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARG) were assessed using real-time qPCR.
Results AZT significantly decreased community diversity with a stronger and more persistent effect in lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for one month after macrolide cessation.
Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella.
Conclusions 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.
Footnotes
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Conflict of interest: Christophe von Garnier reports grants or contracts from Ligue Pulmnoaire Vaudoise, Fondation Yuchum, and Fondation Placide Nicod, outside the submitted work.
Conflict of interest: Sabina Anna Guler reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD, Boehringer Ingelheim, and Roche, outside the submitted work.
Conflict of interest: Manuela Funke-Chambour reports support for the present manuscript Research Fund of the Swiss Lung Association, Bern; grants or contracts from Boehringer Ingelheim, Roche, and CSL Behring, outside the submitted work; consulting fees from Boehringer Ingelheim, and Daiichi Sankyo, outside the submitted work; payment or honoraria from MSD, and Novartis, outside the submitted work.
Conflict of interest: Christian F. Clarenbach reports consulting fees from GSK, Novartis, Vifo, Boehringer, Astra Zeneca, Sanofi, and Daiichi Sankyo, outside the submitted work; payment or honoraria from GSK, Novartis, Vifor, Boehringer, Astra Zeneca, and Sanofi, outside the submitted work; support for attending meetings and/or travel from Boehringer, and Astra Zeneca, outside the submitted work.
Conflict of interest: The remaining authors have nothing to disclose.
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- Received December 18, 2022.
- Accepted February 23, 2023.
- Copyright ©The authors 2023
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