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-
1.
World Health Organization , 2010. Guideline: Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva, Switzerland: WHO.
-
2.
Page A-L et al.2013. Infections in children admitted with complicated severe acute malnutrition in Niger. PLOS One 8: e68699–9.
-
3.
Bourke CD, Berkley JA, Prendergast AJ , 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386–398.
-
4.
Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ , 2013. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 368: 425–435.
-
5.
Isanaka S et al.2016. Routine amoxicillin for uncomplicated severe acute malnutrition in children. N Engl J Med 374: 444–453.
-
6.
Lipsitch M, Samore MH , 2002. Antimicrobial use and antimicrobial resistance: a population perspective. Emerg Infect Dis 8: 347–354.
-
7.
O’Brien K, Emerson P, Hooper PJ, Reingold AL, Dennis EG, Keenan JD, Lietman TM, Oldenburg CE, 2018. Antimicrobial resistance following mass azithromycin distribution for trachoma: a systematic review. Lancet Infect Dis 19: e14–e25.
-
8.
O’Brien KS et al.2021. Comparing azithromycin to amoxicillin in the management of uncomplicated severe acute malnutrition in Burkina Faso: a pilot randomized trial. medRxiv. doi: 10.1101/2021.06.15.21258967.
-
9.
O’Brien K, Sié A, Dah C, Ourohire M, Arzika AM, Boudo V, Lebas E, Godwin WW, Arnold BF, Oldenburg CE , 2021. Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud 7: 97.
-
10.
Crofts TS, Gasparrini AJ, Dantas G , 2017. Next-generation approaches to understand and combat the antibiotic resistome. Nat Rev Microbiol 15: 422–434.
-
11.
Belesova K, Gasparrini A, Sie A, Sauerborn R, Wilkinson P , 2018. Annual crop yield variation, child survival, and nutrition among subsistence farmers in Burkina Faso. Am J Epidemiol 187: 242–250.
-
12.
Oldenburg CE et al.2019. Gut resistome after oral antibiotics in preschool children in Burkina Faso: a randomized controlled trial. Clin Infect Dis 70: 525–527.
-
13.
Lakin SM et al.2016. MEGARes: an antimicrobial resistance database for high throughput sequencing. Nucleic Acids Res 45: D574–D580.
-
14.
Sie A et al.2019. Antibiotic prescriptions among children under age 5 in Nouna District, Burkina Faso. Am J Trop Med Hyg 100: 1121–1124.
-
15.
Sié A et al.2021. Indication for antibiotic prescription among children attending primary healthcare services in Rural Burkina Faso. Clin Infect Dis 1–4: 1288–1291.
-
16.
Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Ndamala CB, Schmicker R, Phiri A, Lufesi N, Izadnegahdar R, May S , 2019. Placebo vs amoxicillin for nonsevere fast-breathing pneumonia in Malawian children aged 2 to 59 months: a double-blind, randomized clinical noninferiority trial. JAMA Pediatr 173: 21–28.
-
17.
van Belkum A, Burnham CAD, Rossen JWA, Mallard F, Rochas O, Dunne WM , 2020. Innovative and rapid antimicrobial susceptibility testing systems. Nat Rev Microbiol 18: 299–311.
-
18.
Keenan JD et al.2018. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med 378: 1583–1592.
-
19.
O’Brien KS et al.2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.
-
20.
Doan T et al.2020. Macrolide and nonmacrolide resistance with mass azithromycin distribution. N Engl J Med 383: 1941–1950.
-
21.
Haug S et al.2010. The decline of pneumococcal resistance after cessation of mass antibiotic distributions for trachoma. Clin Infect Dis 51: 571–574.
-
22.
Bojang A et al.2020. Impact of intrapartum oral azithromycin on the acquired macrolide resistome of infants’ nasopharynx: a randomized controlled trial. Clin Infect Dis 71: 3222–3225.
-
23.
Lipsitch M , 2001. Measuring and interpreting associations between antibiotic use and penicillin resistance in Streptococcus pneumoniae. Clin Infect Dis 32: 1044–1054.
-
24.
Nalwanga D, Musiime V, Kizito S, Kiggundu JB, Batte A, Musoke P, Tumwine JK , 2020. Mortality among children under five years admitted for routine care of severe acute malnutrition: a prospective cohort study from Kampala, Uganda. BMC Pediatr 20: 1–11.
-
25.
Stobaugh HC, Marie N, Mayberry A, Mcgrath M, Mark J, Lelijveld N, 2018. Relapse after severe acute malnutrition: a systematic literature review and secondary data analysis. 1–12. doi: 10.1111/mcn.12702.
-
26.
Oldenburg CE et al.2021. Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: results from a surveillance cohort. BMC Health Serv Res 21: 212.
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Gut Resistome after Antibiotics among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial
Catherine E. Oldenburg
Catherine E. Oldenburg
Francis 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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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 Hinterwirth
Armin Hinterwirth
Francis I Proctor Foundation, University of California, San Francisco, California;
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Millogo Ourohiré
Millogo Ourohiré
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
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Clarisse Dah
Clarisse Dah
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
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Moussa Ouédraogo
Moussa Ouédraogo
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
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Ali Sié
Ali Sié
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
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Valentin Boudo
Valentin Boudo
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso
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Cindi Chen
Cindi Chen
Francis I Proctor Foundation, University of California, San Francisco, California;
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Kevin Ruder
Kevin Ruder
Francis I Proctor Foundation, University of California, San Francisco, California;
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Lina Zhong
Lina Zhong
Francis I Proctor Foundation, University of California, San Francisco, California;
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Elodie Lebas
Elodie Lebas
Francis I Proctor Foundation, University of California, San Francisco, California;
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Fanice Nyatigo
Fanice Nyatigo
Francis I Proctor Foundation, University of California, San Francisco, California;
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Benjamin F. Arnold
Benjamin F. Arnold
Francis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
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Department of Ophthalmology, University of California, San Francisco, California;
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Kieran S. O’Brien
Kieran S. O’Brien
Francis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
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Thuy Doan
Thuy Doan
Francis I Proctor Foundation, 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
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.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization , 2010. Guideline: Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva, Switzerland: WHO.
-
2.
Page A-L et al.2013. Infections in children admitted with complicated severe acute malnutrition in Niger. PLOS One 8: e68699–9.
-
3.
Bourke CD, Berkley JA, Prendergast AJ , 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386–398.
-
4.
Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ , 2013. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 368: 425–435.
-
5.
Isanaka S et al.2016. Routine amoxicillin for uncomplicated severe acute malnutrition in children. N Engl J Med 374: 444–453.
-
6.
Lipsitch M, Samore MH , 2002. Antimicrobial use and antimicrobial resistance: a population perspective. Emerg Infect Dis 8: 347–354.
-
7.
O’Brien K, Emerson P, Hooper PJ, Reingold AL, Dennis EG, Keenan JD, Lietman TM, Oldenburg CE, 2018. Antimicrobial resistance following mass azithromycin distribution for trachoma: a systematic review. Lancet Infect Dis 19: e14–e25.
-
8.
O’Brien KS et al.2021. Comparing azithromycin to amoxicillin in the management of uncomplicated severe acute malnutrition in Burkina Faso: a pilot randomized trial. medRxiv. doi: 10.1101/2021.06.15.21258967.
-
9.
O’Brien K, Sié A, Dah C, Ourohire M, Arzika AM, Boudo V, Lebas E, Godwin WW, Arnold BF, Oldenburg CE , 2021. Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud 7: 97.
-
10.
Crofts TS, Gasparrini AJ, Dantas G , 2017. Next-generation approaches to understand and combat the antibiotic resistome. Nat Rev Microbiol 15: 422–434.
-
11.
Belesova K, Gasparrini A, Sie A, Sauerborn R, Wilkinson P , 2018. Annual crop yield variation, child survival, and nutrition among subsistence farmers in Burkina Faso. Am J Epidemiol 187: 242–250.
-
12.
Oldenburg CE et al.2019. Gut resistome after oral antibiotics in preschool children in Burkina Faso: a randomized controlled trial. Clin Infect Dis 70: 525–527.
-
13.
Lakin SM et al.2016. MEGARes: an antimicrobial resistance database for high throughput sequencing. Nucleic Acids Res 45: D574–D580.
-
14.
Sie A et al.2019. Antibiotic prescriptions among children under age 5 in Nouna District, Burkina Faso. Am J Trop Med Hyg 100: 1121–1124.
-
15.
Sié A et al.2021. Indication for antibiotic prescription among children attending primary healthcare services in Rural Burkina Faso. Clin Infect Dis 1–4: 1288–1291.
-
16.
Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Ndamala CB, Schmicker R, Phiri A, Lufesi N, Izadnegahdar R, May S , 2019. Placebo vs amoxicillin for nonsevere fast-breathing pneumonia in Malawian children aged 2 to 59 months: a double-blind, randomized clinical noninferiority trial. JAMA Pediatr 173: 21–28.
-
17.
van Belkum A, Burnham CAD, Rossen JWA, Mallard F, Rochas O, Dunne WM , 2020. Innovative and rapid antimicrobial susceptibility testing systems. Nat Rev Microbiol 18: 299–311.
-
18.
Keenan JD et al.2018. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med 378: 1583–1592.
-
19.
O’Brien KS et al.2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.
-
20.
Doan T et al.2020. Macrolide and nonmacrolide resistance with mass azithromycin distribution. N Engl J Med 383: 1941–1950.
-
21.
Haug S et al.2010. The decline of pneumococcal resistance after cessation of mass antibiotic distributions for trachoma. Clin Infect Dis 51: 571–574.
-
22.
Bojang A et al.2020. Impact of intrapartum oral azithromycin on the acquired macrolide resistome of infants’ nasopharynx: a randomized controlled trial. Clin Infect Dis 71: 3222–3225.
-
23.
Lipsitch M , 2001. Measuring and interpreting associations between antibiotic use and penicillin resistance in Streptococcus pneumoniae. Clin Infect Dis 32: 1044–1054.
-
24.
Nalwanga D, Musiime V, Kizito S, Kiggundu JB, Batte A, Musoke P, Tumwine JK , 2020. Mortality among children under five years admitted for routine care of severe acute malnutrition: a prospective cohort study from Kampala, Uganda. BMC Pediatr 20: 1–11.
-
25.
Stobaugh HC, Marie N, Mayberry A, Mcgrath M, Mark J, Lelijveld N, 2018. Relapse after severe acute malnutrition: a systematic literature review and secondary data analysis. 1–12. doi: 10.1111/mcn.12702.
-
26.
Oldenburg CE et al.2021. Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: results from a surveillance cohort. BMC Health Serv Res 21: 212.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 922 | 419 | 22 |
| Full Text Views | 138 | 100 | 1 |
| PDF Downloads | 128 | 83 | 1 |