{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:02:06Z","timestamp":1764770526175,"version":"3.46.0"},"reference-count":24,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>Biannual azithromycin administration to preschool children in sub-Saharan Africa improved childhood mortality but selected for antibiotic resistance (AMR). WHO guidelines recommended focusing treatment on infants ages 1\u201311 months old to reduce mortality while minimizing selection of AMR. The Infant Mortality Reduction by the Mass Administration of Azithromycin study was a double-masked, placebo-controlled, cluster-randomized trial that investigated these WHO guidelines. Health centers from three regions of Burkina Faso were randomized in a 2:1 ratio to receive either biannual azithromycin (67%) or placebo (33%) distribution to children 1\u201311 months old. A total of 3,524 rectal samples from children ages 1\u201359 months old from 60 randomly selected communities were included in the analysis. The prespecified primary outcome was the community-level fold change in macrolide resistance determinants between arms at the 24-month time point. Macrolide resistance determinants in the gut of children in communities whose infants received azithromycin did not increase compared with those in communities treated with placebo (1.05-fold change). Similarly, the fold changes for resistance determinants for beta-lactams, metronidazole, sulfonamides, tetracycline, and trimethoprim were 0.99-fold, 1.00-fold, 1.22-fold, 0.96-fold, and 0.96-fold, respectively. At 6 months after the fourth treatment, there were no detectable differences in the microbiome structure (Euclidean permutational multivariate analysis of variance) and Shannon diversity index between treatment arms. These results suggest that biannual azithromycin administration to children 1\u201311 months old did not lead to a significant long-lasting increase in gut AMR or alterations of the gut microbiomes of children 1\u201359 months old in the community.<\/jats:p>","DOI":"10.4269\/ajtmh.25-0238","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T15:39:51Z","timestamp":1761233991000},"page":"1311-1319","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Biannual Azithromycin Distribution to Infants on Community Gut Resistome and Microbiome: A Cluster-Randomized, Controlled Trial"],"prefix":"10.4269","volume":"113","author":[{"given":"Boubacar","family":"Coulibaly","sequence":"first","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisy","family":"Yan","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Si\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiemd\u00e9","family":"Dramane","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamadou","family":"Bountogo","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dah","family":"Clarisse","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ouermi","family":"Lucienne","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny","family":"Yago-Wienne","sequence":"additional","affiliation":[{"name":"Helen Keller International, Dakar, Senegal;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djeinam","family":"Tour\u00e9","sequence":"additional","affiliation":[{"name":"Helen Keller International, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges","family":"Dimith\u00e9","sequence":"additional","affiliation":[{"name":"Helen Keller International, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Khassanov","sequence":"additional","affiliation":[{"name":"Helen Keller International, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souleymane","family":"Sidib\u00e9","sequence":"additional","affiliation":[{"name":"Helen Keller International, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel Pouorinib\u00e9","family":"Som\u00e9","sequence":"additional","affiliation":[{"name":"Helen Keller International, Ouagadougou, Burkina Faso;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zhong","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindi","family":"Chen","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Yu","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YuHeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Abraham","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany","family":"Peterson","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Hinterwirth","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin F.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California;"},{"name":"Institute for Global Health Sciences, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine E.","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Lebas","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Lietman","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California;"},{"name":"Institute for Global Health Sciences, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy","family":"Doan","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","series-title":"N Engl J Med","first-page":"1583","article-title":"Azithromycin to reduce childhood mortality in sub-Saharan Africa","volume":"378","author":"Keenan","year":"2018"},{"key":"b2","series-title":"N Engl J Med","first-page":"2207","article-title":"Longer-term assessment of azithromycin for reducing childhood mortality in Africa","volume":"380","author":"Keenan","year":"2019"},{"key":"b3","series-title":"JAMA","first-page":"482","article-title":"Mass azithromycin distribution to prevent child mortality in Burkina Faso: The CHAT randomized clinical trial","volume":"331","author":"Oldenburg","year":"2024"},{"key":"b4","series-title":"N Engl J Med","first-page":"699","article-title":"Azithromycin to reduce mortality\u2014An adaptive cluster-randomized trial","volume":"391","author":"O\u2019Brien","year":"2024"},{"key":"b5","series-title":"N Engl J Med","first-page":"2271","article-title":"Macrolide resistance in MORDOR I\u2014A cluster-randomized trial in Niger","volume":"380","author":"Doan","year":"2019"},{"key":"b6","series-title":"N Engl J Med","first-page":"1941","article-title":"Macrolide and nonmacrolide resistance with mass azithromycin distribution","volume":"383","author":"Doan","year":"2020"},{"key":"b7","series-title":"PLoS Med","first-page":"e1004386","article-title":"Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR)","volume":"21","author":"Arzika","year":"2024"},{"year":"2020","key":"b8","article-title":"WHO Guideline on Mass Drug Administration of Azithromycin to Children under Five Years of Age to Promote Child Survival."},{"key":"b9","series-title":"Am J Trop Med Hyg","first-page":"291","article-title":"Gut microbiome diversity and antimicrobial resistance after a single dose of oral azithromycin in children: A randomized placebo-controlled trial","volume":"110","author":"Doan","year":"2024"},{"key":"b10","series-title":"Genome Biol","first-page":"257","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"Wood","year":"2019"},{"key":"b11","series-title":"Nucleic Acids Res","first-page":"D574","article-title":"MEGARes: An antimicrobial resistance database for high throughput sequencing","volume":"45","author":"Lakin","year":"2017"},{"key":"b12","series-title":"Nucleic Acids Res","first-page":"D561","article-title":"MEGARes 2.0: A database for classification of antimicrobial drug, biocide and metal resistance determinants in metagenomic sequence data","volume":"48","author":"Doster","year":"2020"},{"key":"b13","series-title":"Genome Biol","first-page":"550","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014"},{"year":"2013","key":"b14","article-title":"R: A Language and Environment for Statistical Computing."},{"article-title":"Vegan: Community Ecology Package.","year":"2024","author":"Jari Oksanen","key":"b15"},{"key":"b16","series-title":"Clin Infect Dis","first-page":"1136","article-title":"Assessment of spillover of antimicrobial resistance to untreated children 7\u201312 years old after mass drug administration of azithromycin for child survival in Niger: A secondary analysis of the MORDOR cluster-randomized trial","volume":"79","author":"Peterson","year":"2024"},{"key":"b17","series-title":"Lancet","first-page":"630","article-title":"Azithromycin in control of trachoma","volume":"354","author":"Schachter","year":"1999"},{"key":"b18","series-title":"Nat Rev Dis Primers","first-page":"32","article-title":"Trachoma","volume":"8","author":"Solomon","year":"2022"},{"year":"1998","key":"b19","article-title":"Report of the Third Meeting of the WHO Alliance for the Global Elimination of Trachoma."},{"key":"b20","series-title":"Lancet Infect Dis","first-page":"e14","article-title":"Antimicrobial resistance following mass azithromycin distribution for trachoma: A systematic review","volume":"19","author":"O\u2019Brien","year":"2019"},{"key":"b21","series-title":"Clin Infect Dis","first-page":"571","article-title":"The decline of pneumococcal resistance after cessation of mass antibiotic distributions for trachoma","volume":"51","author":"Haug","year":"2010"},{"key":"b22","series-title":"Antibiotics (Basel)","first-page":"237","article-title":"Phenotypic resistance to antibiotics","volume":"2","author":"Corona","year":"2013"},{"key":"b23","series-title":"Nat Commun","first-page":"5792","article-title":"Prediction of antibiotic resistance by gene expression profiles","volume":"5","author":"Suzuki","year":"2014"},{"key":"b24","series-title":"Nat Commun","first-page":"4352","article-title":"Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network","volume":"5","author":"L\u00e1z\u00e1r","year":"2014"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1311.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1311.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1311.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T13:32:13Z","timestamp":1764768733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1311.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":24,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.25-0238","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"type":"print","value":"0002-9637"},{"type":"electronic","value":"1476-1645"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}