Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis
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 antimicrobia...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-04-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00103-18 |
| _version_ | 1818824760675532800 |
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| author | Jocelyn M. Choo Guy C. J. Abell Rachel Thomson Lucy Morgan Grant Waterer David L. Gordon Steven L. Taylor Lex E. X. Leong Steve L. Wesselingh Lucy D. Burr Geraint B. Rogers |
| author_facet | Jocelyn M. Choo Guy C. J. Abell Rachel Thomson Lucy Morgan Grant Waterer David L. Gordon Steven L. Taylor Lex E. X. Leong Steve L. Wesselingh Lucy D. Burr Geraint B. Rogers |
| author_sort | Jocelyn M. Choo |
| collection | DOAJ |
| description | 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). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined 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 pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance 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 increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight 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 reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority. |
| first_indexed | 2024-12-19T00:01:00Z |
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| id | doaj.art-9dccb828593f4ef89e2c94eed49f9713 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T00:01:00Z |
| publishDate | 2018-04-01 |
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| spelling | doaj.art-9dccb828593f4ef89e2c94eed49f97132022-12-21T20:46:28ZengAmerican Society for MicrobiologymSphere2379-50422018-04-013210.1128/mSphere.00103-18Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis BronchiectasisJocelyn M. Choo0Guy C. J. Abell1Rachel Thomson2Lucy Morgan3Grant Waterer4David L. Gordon5Steven L. Taylor6Lex E. X. Leong7Steve L. Wesselingh8Lucy D. Burr9Geraint B. Rogers10Infection and Immunity, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaSAHMRI Microbiome Research Laboratory, Flinders University School of Medicine, Adelaide, South Australia, AustraliaGallipoli Medical Research Centre, University of Queensland, Greenslopes Private Hospital, Brisbane, AustraliaDepartment of Respiratory Medicine, Concord Hospital Clinical School, University of Sydney, Sydney, New South Wales, AustraliaSchool of Medicine and Pharmacology Royal Perth Hospital Unit, The University of Western Australia, Perth, AustraliaDepartment of Microbiology and Infectious Diseases, Flinders University, Adelaide, South Australia, AustraliaSAHMRI Microbiome Research Laboratory, Flinders University School of Medicine, Adelaide, South Australia, AustraliaInfection and Immunity, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaInfection and Immunity, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaImmunity, Infection and Inflammation Program, Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, Queensland, AustraliaInfection and Immunity, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaABSTRACT 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). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined 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 pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance 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 increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight 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 reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.https://journals.asm.org/doi/10.1128/mSphere.00103-18antibiotic resistancebronchiectasismacrolide therapyoropharyngeal microbiome |
| spellingShingle | Jocelyn M. Choo Guy C. J. Abell Rachel Thomson Lucy Morgan Grant Waterer David L. Gordon Steven L. Taylor Lex E. X. Leong Steve L. Wesselingh Lucy D. Burr Geraint B. Rogers Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis mSphere antibiotic resistance bronchiectasis macrolide therapy oropharyngeal microbiome |
| title | Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis |
| title_full | Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis |
| title_fullStr | Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis |
| title_full_unstemmed | Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis |
| title_short | Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis |
| title_sort | impact of long term erythromycin therapy on the oropharyngeal microbiome and resistance gene reservoir in non cystic fibrosis bronchiectasis |
| topic | antibiotic resistance bronchiectasis macrolide therapy oropharyngeal microbiome |
| url | https://journals.asm.org/doi/10.1128/mSphere.00103-18 |
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