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Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial.

ABSTRACT: Background:Exposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children. Methods:Children aged 6-59 months were randomized (1:1:1:1) to a 5-day course of 1 of 3 antibiotics, including amoxicillin (25 mg/kg/d twice-daily doses), azithromycin (10 mg/kg dose on day 1 and then 5 mg/kg once daily for 4 days), cotrimoxazole (240 mg once daily), or placebo. Rectal swabs were obtained at baseline and 5 days after the last dose and were processed using 16S rRNA gene sequencing. The prespecified primary outcome was inverse Simpson's ?-diversity index. Results:Post-treatment Simpson's diversity was significantly different across the 4 arms (P = .003). The mean Simpson's ?-diversity among azithromycin-treated children was significantly lower than in placebo-treated children (6.6; 95% confidence interval [CI], 5.5-7.8; vs 9.8; 95% CI, 8.7-10.9; P = .0001). Diversity in children treated with amoxicillin (8.3; 95% CI, 7.0-9.6; P = .09) or cotrimoxazole (8.3; 95% CI, 8.2-9.7; P = .08) was not significantly different than placebo. Conclusions:Azithromycin affects the composition of the pediatric intestinal microbiome. The effect of amoxicillin and cotrimoxazole on microbiome composition was less clear. Clinical Trials Registration:clinicaltrials.gov NCT03187834.

SUBMITTER: Oldenburg CE

PROVIDER: S-EPMC6262116 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial.

Oldenburg Catherine E CE Sié Ali A Coulibaly Boubacar B Ouermi Lucienne L Dah Clarisse C Tapsoba Charlemagne C Bärnighausen Till T Ray Kathryn J KJ Zhong Lina L Cummings Susie S Lebas Elodie E Lietman Thomas M TM Keenan Jeremy D JD Doan Thuy T

Open forum infectious diseases 20181102 11

<h4>Background</h4>Exposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children.<h4>Methods</h4>Children aged 6-59 months were randomized (1:1:1:1) to a 5-day course of 1 of 3 antibiotics, i ...[more]

PMID: 30515431

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Project description:BackgroundIn low- and middle-income countries, the prevalence of antimicrobial resistance (AMR) is increasing. To control AMR, WHO recommends monitoring antibiotic use, in particular Watch antibiotics. These are critically important antibiotics, with restricted use because at risk of becoming ineffective due to increasing AMR. We investigated pre-hospital antibiotic use in rural Burkina Faso.MethodsDuring 2016-2017, we collected data from patients aged > 3 months presenting with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, including antibiotic use in the two weeks prior to consultation or hospitalization. We analysed reported antibiotic use by applying the WHO Access, Watch, Reserve classification.ResultsOf 920 febrile participants (63.0% ≤ 14 years), pre-hospital antibiotic use was reported by 363 (39.5%). Among these 363, microbiological diagnoses were available for 275 (75.8%) patients, of whom 162 (58.9%) were non-bacterial infections. Use of more than one antibiotic was reported by 58/363 (16.0%) participants. Of 491 self-referred patients who did not previously visit a primary health care center, 131 (26.7%) reported antibiotic use. Of 424 antibiotics reported, 265 (62.5%) were Access and 159 (37.5%) Watch antibiotics. Watch antibiotic use was more frequent among patients > 14 year olds (51.1%) compared to those 0-14 year old (30.7%, p < 0.001) and among referrals from the primary health care centers (42.2%) compared to self-referred patients (28.1%, p = 0.004). Most frequently reported Watch antibiotics were ceftriaxone (114, 71.7%) and ciprofloxacin (32, 20.1%).ConclusionThe reported frequent use of Watch group antibiotics among febrile patients prior to presentation to the hospital in rural Burkina Faso highlights the need to develop targeted interventions to improve antibiotic use in community settings as part of strengthening antibiotic stewardship in low- and middle-income countries. This should include facilitating referral, access to qualified prescribers and diagnostic tools in rural primary health care centers. Trial registration ClinicalTrials.gov identifier: NCT02669823. Registration date was February 1, 2016.

Dataset Information

Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial.

Publications

Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial.

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