Macrolide therapy for chronic lung disease: significant implications for oropharyngeal dysbiosis and the selection of resistance — ASN Events
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  2. Poster Session C
  3. Macrolide therapy for chronic lung disease: significant implications for oropharyngeal dysbiosis and the selection of resistance

Macrolide therapy for chronic lung disease: significant implications for oropharyngeal dysbiosis and the selection of resistance (#423)

Jocelyn M Choo* 1 , Lex EX Leong* 1 , David J Serisier 2 3 , Geraint B Rogers 1
  1. SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, South Australia, Australia
  2. Immunity, Infection and Inflammation Program, Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia
  3. Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Queensland, Australia

Macrolide antibiotics are used increasingly to prevent recurrent exacerbations in patients with chronic lung diseases due to their clinical efficacy across a range of respiratory conditions. However, the impact of their long-term use on wider commensal systems, such as those within the oropharynx, is not known. There are serious concerns regarding the implications of prolonged antibiotic exposure on both the disruption of commensal microbiota, and the potential transmission of antibiotic resistant pathogens.

To investigate the impact of macrolide use on commensal microbiota, culture independent analysis was performed on oropharyngeal swabs collected from patients with non-cystic fibrosis bronchiectasis, as part of a randomised controlled trial of low-dose erythromycin therapy. Paired-end 16S rRNA gene sequencing, targeting the V1-V3 region, was used to characterise oropharyngeal microbiota composition in 30 patients following four weeks of erythromycin or placebo treatment. Changes in macrolide resistance gene carriage (ermA, ermB, ermB, mef and msrA) were firstly determined using a robust multiplex PCR screen, and then by quantitative PCR normalised to the total bacterial load. 

Patients who received erythromycin had significantly reduced oropharyngeal microbiota evenness (Simpson index, p<0.001, t-test) and diversity (Shannon index, p=0.001, t-test), with the most substantial contributions to compositional change made by taxa within the Firmicutes, Bacteroidetes and Fusobacteria phyla. Quantitative PCR analysis indicated that erythromycin exposure resulted in a significant increase in macrolide resistance gene carriage (p<0.05, Wilcoxon test), with changes seen in several resistance determinants.

Despite the low dose and the relatively short period of treatment, these data revealed that macrolide therapy have profound disruptive effects on the oropharyngeal microbiota and strongly selects for resistance carriage. These findings highlight the potential for systemic antibiotics to trigger dysbiosis in commensal bacterial populations, a potentially important phenomenon that received relatively little clinical consideration.

* Co-first authors 

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