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Gut Resistome after Antibiotics among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial

Catherine E. OldenburgFrancis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology and Biostatistics, 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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Millogo OurohiréCentre de Recherche en Santé de Nouna, Nouna, Burkina Faso

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

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Moussa OuédraogoCentre 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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Valentin BoudoCentre 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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Kevin RuderFrancis 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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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.

A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6–59 months of age with uncomplicated SAM (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < −3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65% azithromycin, 65% placebo, odds ratio, OR, 1.00, 95% confidence interval, CI, 0.43–2.34) or beta-lactam resistance determinants (82% azithromycin, 83% amoxicillin, OR 0.94, 95% CI, 0.33–2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.

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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 94143. E-mail: catherine.oldenburg@ucsf.edu

Financial support: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD R21 HD100932, PI: Oldenburg) and the University of California, San Francisco Resource Allocation Program (RAP). The funders played no role in the design of the study, 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, and Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, E-mail: catherine.oldenburg@ucsf.edu. Armin Hinterwirth, Cindi Chen, Kevin Ruder, Lina Zhong, 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, kevin.ruder@ucsf.edu, lina.zhong@ucsf.edu, elodie.lebas@ucsf.edu, and fanice.nyatigo@ucsf.edu. Millogo Ourohiré, Clarisse Dah, Moussa Ouédraogo, Ali Sié, and Valentin Boudo, Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso, E-mails: ourohire2001@yahoo.fr, n.clarissedah@yahoo.fr, moussaoued0202@gmail.com, sieali@yahoo.fr, and valentinboudo@gmail.com. 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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