Indirect Effect of Azithromycin Use on the Intestinal Microbiome Diversity of Untreated Children: A Randomized Trial.
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SUBMITTER: Oldenburg CE
PROVIDER: S-EPMC6420410 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Indirect Effect of Azithromycin Use on the Intestinal Microbiome Diversity of Untreated Children: A Randomized Trial.
Oldenburg Catherine E CE Sié Ali A Coulibaly Boubacar B Ouermi Lucienne L Dah Clarisse C Tapsoba Charlemagne C Bärnighausen Till T Lebas Elodie E Arzika Ahmed M AM Cummings Susie S Zhong Lina L Lietman Thomas M TM Keenan Jeremy D JD Doan Thuy T
Open forum infectious diseases 20190206 3
Cohabiting children may share components of their intestinal microbiome. We evaluated whether receipt of azithromycin in one sibling confers changes to the intestinal microbiome in an untreated sibling compared with placebo in a randomized controlled trial. We found no evidence of an indirect effect of antibiotic use in cohabiting children. <b>Clinical Trials Registrations:</b> NCT03187834. ...[more]
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Project description:BackgroundAntibiotic use by one individual may affect selection for antimicrobial resistance in close contacts. Here we evaluated whether oral antibiotic treatment of one child within a household affected the gut resistome of an untreated cohabiting child.MethodsHouseholds with at least two children <5 y of age were randomized in a 1:1 fashion to a 5d course of azithromycin or placebo. To evaluate indirect effects of azithromycin treatment on the gut resistome, we randomly assigned one child in the house to azithromycin and one to placebo. In placebo households, each child received placebo. We performed DNA sequencing of rectal swabs collected 5 d after the last antibiotic dose. We estimated risk ratios for the presence of genetic resistance determinants at the class level using modified Poisson models for children in azithromycin households compared with placebo households and assessed the composition of the resistome using permutational analysis of variance (PERMANOVA).ResultsOf 58 children (n = 30 azithromycin households, n = 28 placebo households) with post-treatment rectal swabs, genetic resistance determinants were common but there was no significant difference at the class (p = 0.54 for macrolides) or gene (p = 0.94 for structure by PERMANOVA, p = 0.94 for diversity) level between untreated children in azithromycin households compared with placebo households.ConclusionsThe results are encouraging that one child's antibiotic use may not influence the resistome of another child. Trial registration: ClinicalTrials.gov NCT03187834.
| S-EPMC7902679 | biostudies-literature
Project description:PurposeThe aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area.MethodsIn this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms.ResultsOne thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin ( P = 0.0003). Neisseria gonorrhoeae , Neisseria lactamica , and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms ( P = 0.63), but mefA / E was increased ( P = 0.04) in the azithromycin-treated arm.ConclusionsWe found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.
| S-EPMC8894504 | biostudies-literature
Project description:Feces samples collected from healthy and asthmatic children, sequenced by method of High throughput sequencing for 16SrRNA genes. Raw sequence reads
| PRJNA532496 | ENA
Project description:Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
| S-EPMC4737757 | biostudies-literature
Project description:BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical trials registrationNCT02048007.
| S-EPMC6101535 | biostudies-literature
Project description:BackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities. This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.ResultsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.ConclusionsMDA with azithromycin increased carriage of macrolide-resistant bacteria, but had limited impact on clinically relevant bacteria. However, increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage. Trial registration ClinicalTrial.gov, NCT02047981. Registered January 29th 2014, https://clinicaltrials.gov/ct2/show/NCT02047981.
| S-EPMC8740015 | biostudies-literature
Project description:Experimental Design Type of experiment: In order to evaluate the influence of subinhibitory concentrations of the macrolide antibiotic Azithromycin (AZM) on the global Pseudomonas aeruginosa gene expression, we performed a comparative gene expression analysis of AZM-treated versus untreated P. aeruginosa PAO1 cultures. Experimental factors: P. aeruginosa PAO1 cultures with and without addition of 2 µg/ ml AZM were grown until early stationary phase. Total RNA was extracted when the cultures reached an OD600 of 2.8. The transcriptomes of the untreated cultures were taken as reference values. Both of the AFFYMETRIX Chips of AZM-treated PAO1 (GSM45590, GSM45591) were compared with each of the two chips of the untreated PAO1 (GSM45588, GSM45589). Hybridization procedures and parameters: Hybridization of the probes was carried out according to the manufacturer’s “Expression Analysis Protocol (p. 25: Modified Fluidic Protocol for P. aeruginosa cDNA Assay)”, see http://www.affymetrix.com: Hybridization for 16 h at 50°C and 60 rpm. - Post Hyb Wash 1: 10 cycles of 2 mixes/cycle with Wash Buffer A at 25°C - Post Hyb Wash 2: 4 cycles of 15 mixes/cycle with Wash Buffer B at 50°C - Stain: Stain the probe array for 10 minutes in Streptavidin Solution Mix at 25°C - Post Stain Wash: 10 cycles of 4 mixes/cycle with Wash Buffer A at 30°C - 2nd Stain Wash: Stain the probe array for 10 minutes in antibody solution at 25°C - 3rd Stain Wash: Stain the probe array for 10 minutes in SAPE solution at 25°C - Final Wash: 15 cycles of 4 mixes/cycle with Wash Buffer A at 30°C. The holding temperature is 25°C. Measurement of data and specifications: Data transformation and selection procedures: · The entire signals were scaled to 150 (4% capped median); scaling factors of the arrays were within 3.4 fold of each other, as the % genes called present were in the range of 23.7% and 38.1% for three arrays (GSM455889, GSM45589, GSM45591) and 74,4% for one array (GSM45590). The background levels (Average Background) were similar for all arrays (in a range of 47.20 and 55.64). The Q scores were comparable (in a range of 2.38 and 2.81). The Average Signals of the four arrays were similar (between 187.8 and 228.7). · Scanning hardware: AFFYMETRIX Scanner; software: AFFYMETRIX MAS 5 (Statistical Algorithms Reference Guide, http://www.affymetrix.com/support/technical/technotes/statistical_reference_guide.pdf), MICRO DB 3 and DMT 3 · Image analysis software: AFFYMETRIX MAS 5 Data selection: · Threshold of Signal Log ratio: -1/1; change is I (increased), MI (marginally increased), D (decreased), MD (marginally decreased); change p-value >0.999 or <0.001; only genes that are present (Detection=P) in at least one of the compared chipsets. · Only following genes were considered: Minimal threshold of regulation ±2 fold; minimal change p-values of 0.999 and 0.001, respectively; minimal difference of signal intensities of 200. · The final gene expression data table used by the authors to make their conclusions after data selection and transformation will be published as supplementary data. Keywords: other
2006-05-10 | GSE2430 | GEO
Project description:The intestinal microbiome was examined from fecal pellets of animals with genetic targeting of the BTLA inhibitory receptor and the TNFR superfamily member HVEM, or in animals treated with agonist antibodies specific for BTLA.
2022-02-08 | GSE195890 | GEO
Project description:Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in chronic obstructive pulmonary disease patients with emphysema. The antimicrobial effects of AZM on the lung microbiome are not known and may contribute to its beneficial effects. Methods. Twenty smokers with emphysema were randomized to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements included: rDNA gene quantity and sequence. Results. Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Conclusions. AZM treatment the lung microbiome Randomized trial comparing azithromycin (AZM) treatment with placebo for eight weeks. Bronchoalveolar lavage (BAL) samples were obtained before and after treatment to explore the effects of AZM on microbiome, in the lower airways. 16S rRNA was quantified and sequenced (MiSeq) The amplicons from total 39 samples are barcoded and the barcode is provided in the metadata_complete.txt file.
2016-07-19 | E-GEOD-74396 | biostudies-arrayexpress
Project description:Community-level mass treatment with azithromycin has been associated with a mortality benefit in children. However, antibiotic exposures result in disruption of the gut microbiota and repeated exposures may reduce recovery of the gut flora. We conducted a nested cohort study within the framework of a randomized controlled trial to examine associations between mass drug administration (MDA) with azithromycin and the gut microbiota of rural Malawian children aged between 1 and 59 months. Fecal samples were collected from the children at baseline and 6 months after two or four biannual rounds of azithromycin treatment. DNA was extracted from fecal samples and V4-16S rRNA sequencing used to characterize the gut microbiota. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were the dominant phyla while Faecalibacterium and Bifidobacterium were the most prevalent genera. There were no associations between azithromycin treatment and changes in alpha diversity, however, four biannual rounds of treatment were associated with increased abundance of Prevotella. The lack of significant changes in gut microbiota after four biannual treatments supports the use of mass azithromycin treatment to reduce mortality in children living in low- and middle-income settings.
| S-EPMC8885630 | biostudies-literature