Impact of long-term erythromycin therapy on the oropharyngeal microbiome and resistance gene reservoir in non-cystic fibrosis bronchiectasis

Published 18 April 2018Long-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.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. Roger

Elucidation of fundamental properties of helium in metals by nuclear magnetic resonance techniques

The nuclear magnetic resonance (NMR) properties of very high density {sup 3}He in metals are discussed in the context of the corresponding properties in relatively high density bulk {sup 3}He. In particular, the effects of the {sup 3}He diffusion on the contribution of the {sup 3}He-{sup 3}He dipolar interaction to the lineshape and to the spin-lattice relaxation parameter (T{sub 1}) are described. It is shown that the temperature dependence of the lineshape and of T{sub 1} are independent sources of information about helium density and also about helium diffusivity. Moreover, T{sub 1} is shown to be a sensitive indicator of melting transitions in bulk {sup 3}He. Palladium tritide is presented as a model system for NMR studies of {sup 3}He in metals. Experimental NMR studies of this system reveal behavior analogous to what has been observed for bulk helium. Evidence for a {sup 3}He phase transition near 250 K is provided by the temperature dependence of T{sub 1}. Assuming this to be a melting transition, a density is obtained from the bulk helium EOS that is in good agreement with theory and with swelling measurements on related metal tritides. {sup 3}He NMR measurements have also provided information about the density distribution, helium diffusivity, and mean bubble size in palladium tritide. 22 refs., 8 figs

Forestry development prospects in the Imatong Central Forest Reserve, Southern Sudan: volume 2 (main report): Land resource study no.28 (2)

An area of nearly 10000 ha has been demarcated in the Ngairigi and Upper Kinyeti Basins for the development of softwood plantations. Some 6 000 ha of the area selected has been designated Class 1 land, having no or only minor limitations for plantation development. An enumeration of 490.8 ha of existing plantations has revealed a standing volume of 127 000 m3. Recommendations are made for clear felling 274.8 ha, which can be expected to yield about 84 900 m3, for thinning 152.2 ha, which would yield about 9 800 m3, for pruning 99.4 ha and for weeding, cleaning and beating up 60.0 ha. Of the area selected for plantation development, 6405.6 ha are covered by vegetation types containing merchantable timber species. These types include Croton - Macaranga - Albizia forest, Olea - Podocarpus closed forest, Podocarpus - Syzygium open forest and Podocarpus - Dombeya open forest and together they contain about 841 500 m3 of timber of which 186000 m3 is Podocarpus and 203600 m3 is established hardwoods. An enumeration of the Talanga forest showed that there was a standing volume of about 258500 m3 over some 2 135.7 ha, and this would keep the Katire sawmill supplied with timber for between 5 and 11 years, depending upon the area over which it proved possible to extract economically

Forestry development prospects in the Imatong Central Forest Reserve, Southern Sudan: volume 1 (summary)

This report is issued with the permission of the Sudanese Government and covers the selection of accessible areas within the Imatong Central Forest Reserve suitable for the establishment of 10 000 ha of softwood plantations, the assessment of the forest likely to be cleared during the establishment of the new plantations, the assessment of the existing softwood plantations and the assessment of forest areas suitable for exploitation by the Katire sawmill. The fieldwork was undertaken between January and April 1976 and an interim report was issued in May 1976 (Jenkin et al., 1976). In 1974, following a visit to the area by the British Ministry of Overseas Development's (ODM's) Forestry Adviser, the Southern Regional Authorities asked ODM for help in developing the Reserve; a pre-appraisal mission organised jointly by the Commonwealth Development Corporation (CDC), ODM and the Sudanese Government visited the area in November 1975. It was that mission that prepared the detailed terms of reference (Dorward et al., 1976) for the present study.</p

Forestry development prospects in the Imatong Central Forest Reserve, Southern Sudan: volume 3 (maps)

An area of nearly 10000 ha has been demarcated in the Ngairigi and Upper Kinyeti Basins for the development of softwood plantations. Some 6 000 ha of the area selected has been designated Class 1 land, having no or only minor limitations for plantation development. An enumeration of 490.8 ha of existing plantations has revealed a standing volume of 127 000 m3. Recommendations are made for clear felling 274.8 ha, which can be expected to yield about 84 900 m3, for thinning 152.2 ha, which would yield about 9 800 m3, for pruning 99.4 ha and for weeding, cleaning and beating up 60.0 ha. Of the area selected for plantation development, 6405.6 ha are covered by vegetation types containing merchantable timber species. These types include Croton - Macaranga - Albizia forest, Olea - Podocarpus closed forest, Podocarpus - Syzygium open forest and Podocarpus - Dombeya open forest and together they contain about 841 500 m3 of timber of which 186000 m3 is Podocarpus and 203600 m3 is established hardwoods. An enumeration of the Talanga forest showed that there was a standing volume of about 258500 m3 over some 2 135.7 ha, and this would keep the Katire sawmill supplied with timber for between 5 and 11 years, depending upon the area over which it proved possible to extract economically.</p

Forestry development prospects in the Imatong Central Forest Reserve, Southern Sudan: volume 2 (main report)

An area of nearly 10000 ha has been demarcated in the Ngairigi and Upper Kinyeti Basins for the development of softwood plantations. Some 6 000 ha of the area selected has been designated Class 1 land, having no or only minor limitations for plantation development. An enumeration of 490.8 ha of existing plantations has revealed a standing volume of 127 000 m3. Recommendations are made for clear felling 274.8 ha, which can be expected to yield about 84 900 m3, for thinning 152.2 ha, which would yield about 9 800 m3, for pruning 99.4 ha and for weeding, cleaning and beating up 60.0 ha. Of the area selected for plantation development, 6405.6 ha are covered by vegetation types containing merchantable timber species. These types include Croton - Macaranga - Albizia forest, Olea - Podocarpus closed forest, Podocarpus - Syzygium open forest and Podocarpus - Dombeya open forest and together they contain about 841 500 m3 of timber of which 186000 m3 is Podocarpus and 203600 m3 is established hardwoods. An enumeration of the Talanga forest showed that there was a standing volume of about 258500 m3 over some 2 135.7 ha, and this would keep the Katire sawmill supplied with timber for between 5 and 11 years, depending upon the area over which it proved possible to extract economically.</p