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Gut Microbiome among Children with Uncomplicated Severe Acute Malnutrition in a Randomized Controlled Trial of Azithromycin versus Amoxicillin

Catherine E. OldenburgFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology & Biostatistics, University of California, San Francisco, California;
Institute for Global Health Sciences, University of California, San Francisco, California;

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Armin HinterwirthFrancis I Proctor Foundation, University of California, San Francisco, California;

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Clarisse DahCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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Ourohiré MillogoCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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Boubacar CoulibalyCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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Moussa OuedraogoCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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Ali SiéCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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Cindi ChenFrancis I Proctor Foundation, University of California, San Francisco, California;

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Lina ZhongFrancis I Proctor Foundation, University of California, San Francisco, California;

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Kevin RuderFrancis I Proctor Foundation, University of California, San Francisco, California;

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Elodie LebasFrancis I Proctor Foundation, University of California, San Francisco, California;

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Fanice NyatigoFrancis I Proctor Foundation, University of California, San Francisco, California;

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Benjamin F. ArnoldFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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Kieran S. O’BrienFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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Thuy DoanFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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ABSTRACT.

Antibiotics are routinely used as part of the management of severe acute malnutrition and are known to reduce gut microbial diversity in non-malnourished children. We evaluated gut microbiomes in children participating in a randomized controlled trial (RCT) of azithromycin versus amoxicillin for severe acute malnutrition. Three hundred one children aged 6 to 59 months with uncomplicated severe acute malnutrition (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < −3 without clinical complications) were enrolled in a 1:1 RCT of single-dose azithromycin versus a 7-day course of amoxicillin (standard of care). Of these, 109 children were randomly selected for microbiome evaluation at baseline and 8 weeks. Rectal swabs were processed with metagenomic DNA sequencing. We compared alpha diversity (inverse Simpson’s index) at 8 weeks and evaluated relative abundance of microbial taxa using DESeq2. Of 109 children enrolled in the microbiome study, 95 were followed at 8 weeks. We found no evidence of a difference in alpha diversity between the azithromycin and amoxicillin groups at 8 weeks controlling for baseline diversity (mean difference −0.6, 95% CI −1.8 to 0.6, P = 0.30). Gut microbiomes did not diversify during the study. Differentially abundant genera at the P < 0.01 level included Salmonella spp. and Shigella spp., both of which were overabundant in the azithromycin compared with amoxicillin groups. We found no evidence to support an overall difference in gut microbiome diversity between azithromycin and amoxicillin among children with uncomplicated severe acute malnutrition, but potentially pathogenic bacteria that can cause invasive diarrhea were more common in the azithromycin group.

Trial Registration: ClinicalTrials.gov NCT03568643.

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Author Notes

Address correspondence to Catherine E. Oldenburg, Francis I Proctor Foundation, University of California, 490 Illinois St., Floor 2, San Francisco, CA 94158. E-mail: catherine.oldenburg@ucsf.edu

Financial support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Development (R21 HD100932) and the University of California, San Francisco Resource Allocation Program (RAP). The funders did not play a role in study design, analysis, interpretation of data, or decision to publish.

Authors’ addresses: Catherine E. Oldenburg, Francis I Proctor Foundation, University of California, San Francisco, CA, Department of Ophthalmology, University of California, San Francisco, CA, Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, and Institute for Global Health Sciences, University of California, San Francisco, CA, E-mail: catherine.oldenburg@ucsf.edu. Armin Hinterwirth, Cindi Chen, Lina Zhong, Kevin Ruder, Elodie Lebas, and Fanice Nyatigo, Francis I Proctor Foundation, University of California, San Francisco, CA, E-mails: armin.hinterwirth@ucsf.edu, cindi.chen@ucsf.edu, lina.zhong@ucsf.edu, kevin.ruder@ucsf.edu, elodie.lebas@ucsf.edu, and fanice.nyatigo@ucsf.edu. Clarisse Dah, Ourohiré Millogo, Boubacar Coulibaly, Moussa Ouedraogo, and Ali Sié, Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso, E-mails: n.clarissedah@yahoo.fr, ourohire2001@yahoo.fr, boubacar@fasonet.bf, moussaoued0202@gmail.com, and sieali@yahoo.fr. Benjamin F. Arnold, Kieran S. O’Brien, and Thuy Doan, Francis I Proctor Foundation, University of California, San Francisco, CA, and Department of Ophthalmology, University of California, San Francisco, CA, E-mails: ben.arnold@ucsf.edu, kieran.obrien@ucsf.edu, and thuy.doan@ucsf.edu.

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