Long-term macrolide therapy is being used increasingly to reduce rates of exacerbation in patients with chronic respiratory diseases. However, the potential impact of macrolide therapy on the composition of the oropharyngeal microbiota, and the carriage of potentially transmissible macrolide resistance, is of concern.
We analysed oropharyngeal swabs from 84 subjects from the BLESS randomised controlled trial of low-dose erythromycin in adults with bronchiectasis (43 treatment and 41 controls). Oropharyngeal microbiota composition and resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR-based assays.
Twelve month erythromycin therapy resulted in a significant increase in the relative abundance of two taxa related to Haemophilus parainfluenzae within the oropharynx, and significant decreases in the relative abundance of a Streptococcus pseudopneumoniae assigned OTU, three Actinomyces odontolyticus related OTUs and one novel OTU within the genera Actinomyces. While the rates of macrolide resistance genes detection (erm(A), erm(B), erm(C), msrA and mefA/E) did not change significantly following erythromycin treatment, a significant increase in the proportion of bacteria carrying erm(B) and mefA/E was observed. Combining resistance gene detection data with previously reported culture-based streptococcal sensitivity testing indicated that carriage of macrolide resistance determinants extended beyond oropharyngeal streptococci.
Prolonged low-dose erythromycin exposure results in significant changes in the composition of the oropharyngeal microbiota. The clinical significance of these changes is not yet known, however increased carriage of multiple transmissible macrolide resistance determinants within these microbiota highlights the potential macrolide therapy to contribute to community resistance.