Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis Jocelyn M. Choo, a,b Guy C. J. Abell, b Rachel Thomson, c Lucy Morgan, d Grant Waterer, e David L. Gordon, f Steven L. Taylor, b Lex E. X. Leong, a,b Steve L. Wesselingh, a Lucy D. Burr, g,h Geraint B. Rogers a,b a Infection and Immunity, South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia b SAHMRI Microbiome Research Laboratory, Flinders University School of Medicine, Adelaide, South Australia, Australia c Gallipoli Medical Research Centre, University of Queensland, Greenslopes Private Hospital, Brisbane, Australia d Department of Respiratory Medicine, Concord Hospital Clinical School, University of Sydney, Sydney, New South Wales, Australia e School of Medicine and Pharmacology Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia f Department of Microbiology and Infectious Diseases, Flinders University, Adelaide, South Australia, Australia g Immunity, Infection and Inflammation Program, Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia h Department of Respiratory Medicine, Mater Health Services, South Brisbane, Queensland, Australia ABSTRACT Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropha- ryngeal microbiota composition and macrolide resistance gene carriage were deter- mined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneu- moniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the se- quencing results by quantitative PCR confirmed a significant decrease in the abun- dance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin in- creased significantly (P  0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are mod- est and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota high- light the potential for this microbial system to act as a reservoir for resistance. IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might Received 23 February 2018 Accepted 29 March 2018 Published 18 April 2018 Citation Choo JM, Abell GCJ, Thomson R, Morgan L, Waterer G, Gordon DL, Taylor SL, Leong LEX, Wesselingh SL, Burr LD, Rogers GB. 2018. Impact of long-term erythromycin therapy on the oropharyngeal microbiome and resistance gene reservoir in non-cystic fibrosis bronchiectasis. mSphere 3:e00103-18. https:// doi.org/10.1128/mSphere.00103-18. Editor Mariana Castanheira, JMI Laboratories © Crown copyright 2018. This is an open- access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to Geraint B. Rogers, geraint.rogers@sahmri.com. J.M.C. and G.C.J.A. contributed equally to this article. RESEARCH ARTICLE Host-Microbe Biology crossm March/April 2018 Volume 3 Issue 2 e00103-18 msphere.asm.org 1 on May 20, 2018 by guest http://msphere.asm.org/ Downloaded from