{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:44:18Z","timestamp":1783748658477,"version":"3.55.0"},"reference-count":19,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"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":[[2023,11,1]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Azithromycin mass drug administration decreases child mortality but also selects for antibiotic resistance. Herein, we evaluate macrolide resistance of nasopharyngeal <jats:italic>Streptococcus pneumoniae<\/jats:italic> after azithromycin MDA. In a cluster-randomized trial, children 1\u201359 months received azithromycin or placebo biannually. Fifteen villages from each arm were randomly selected for antimicrobial resistance testing, and 10\u201315 randomly selected swabs from enrolled children at each village were processed for <jats:italic>S. pneumoniae<\/jats:italic> isolation and resistance testing. The primary prespecified outcome was macrolide resistance fraction for azithromycin versus placebo villages at 36 months. Secondary non-prespecified outcomes were comparisons of azithromycin and placebo for: 1) macrolide resistance at 12, 24, and 36 months; 2) nonmacrolide resistance at 36 months; and 3) suspected-<jats:italic>erm<\/jats:italic> mutation. At 36 months, 423 swabs were obtained and 322 grew <jats:italic>S. pneumoniae<\/jats:italic>, (azithromycin: 146\/202, placebo: 176\/221). Mean resistance prevalence was non-significantly higher in treatment than placebo (mixed-effects model: 14.6% vs. 8.9%; OR = 2.0, 95% CI: 0.99\u20133.97). However, when all time points were evaluated, macrolide resistance prevalence was significantly higher in the azithromycin group (\u03b2 = 0.102, 95% CI: 0.04\u20130.167). For all nonmacrolides, resistance prevalence at 36 months was not different between the two groups. Azithromycin and placebo were not different for suspected-<jats:italic>erm<\/jats:italic> mutation prevalence. Macrolide resistance was higher in the azithromycin group over all time points, but not at 36 months. Although this suggests resistance may not continue to increase after biannual MDA, more studies are needed to clarify when MDA can safely decrease mortality and morbidity in lower- and middle-income countries.<\/jats:p>","DOI":"10.4269\/ajtmh.23-0431","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T14:32:17Z","timestamp":1696257137000},"page":"1107-1112","source":"Crossref","is-referenced-by-count":14,"title":["Temporal Trends in Phenotypic Macrolide and Nonmacrolide Resistance for Streptococcus pneumoniae Nasopharyngeal Samples Up to 36 Months after Mass Azithromycin Administration in a Cluster-Randomized Trial in Niger"],"prefix":"10.4269","volume":"109","author":[{"given":"Ashley","family":"Hazel","sequence":"first","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Arzika","sequence":"additional","affiliation":[{"name":"The Carter Center, Niamey, Niger;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amza","family":"Abdou","sequence":"additional","affiliation":[{"name":"Programme Nationale de Sant\u00e9 Oculaire, Niamey, Niger;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Lebas","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis C.","family":"Porco","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramatou","family":"Maliki","sequence":"additional","affiliation":[{"name":"The Carter Center, Niamey, Niger;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy","family":"Doan","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Lietman","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"Keenan","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Blumberg","sequence":"additional","affiliation":[{"name":"F. I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"School of Medicine, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"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":"Clin Infect Dis","first-page":"743","article-title":"A cluster-randomized trial to assess the efficacy of targeting trachoma treatment to children","volume":"64","author":"Amza","year":"2017"},{"key":"b4","series-title":"Cochrane Database Syst Rev","first-page":"CD001860","article-title":"Antibiotics for trachoma","volume":"9","author":"Evans","year":"2019"},{"key":"b5","series-title":"PLoS Med","first-page":"e1002835","article-title":"Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: a cluster-randomized, placebo-controlled trial","volume":"16","author":"Arzika","year":"2019"},{"key":"b6","series-title":"Clin Infect Dis","first-page":"e2379","article-title":"The duration of protection from azithromycin against malaria, acute respiratory, gastrointestinal, and skin infections when given alongside seasonal malaria chemoprevention: secondary analyses of data from a clinical trial in Hound\u00e9, Burkina Faso, and Bougouni, Mali","volume":"73","author":"Phiri","year":"2021"},{"key":"b7","series-title":"Infect Dis Poverty","first-page":"77","article-title":"Mass drug administration of antibacterials: weighing the evidence regarding benefits and risks","volume":"11","author":"Rolfe","year":"2022"},{"key":"b8","series-title":"Clin Microbiol Infect","first-page":"326","article-title":"Mass drug administration of azithromycin: an analysis","volume":"29","author":"Kahn","year":"2023"},{"key":"b9","series-title":"N Engl J Med","first-page":"2271","article-title":"Macrolide resistance in MORDOR I \u2014 a cluster-randomized trial in Niger","volume":"380","author":"Doan","year":"2019"},{"key":"b10","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":"b11","series-title":"Nat Med","first-page":"1370","article-title":"Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution","volume":"25","author":"Doan","year":"2019"},{"key":"b12","series-title":"J R Stat Soc B","first-page":"289","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995"},{"key":"b13","year":"2022"},{"key":"b14","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":"b15","series-title":"Clin Infect Dis","first-page":"1519","article-title":"Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young children 6 months after treatment","volume":"56","author":"Coles","year":"2013"},{"key":"b16","series-title":"Trends Microbiol","first-page":"438","article-title":"The rise and fall of antimicrobial resistance","volume":"9","author":"Lipsitch","year":"2001"},{"key":"b17","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":"b18","series-title":"PLoS One","first-page":"e29407","article-title":"The fitness cost of antibiotic resistance in Streptococcus pneumoniae: insight from the field","volume":"7","author":"Maher","year":"2012"},{"key":"b19","series-title":"Proc Natl Acad Sci USA","first-page":"29063","article-title":"The role of \u201cspillover\u201d in antibiotic resistance","volume":"117","author":"Olesen","year":"2020"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/5\/article-p1107.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/109\/5\/article-p1107.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/109\/5\/article-p1107.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:45:10Z","timestamp":1698846310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/109\/5\/article-p1107.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,1]]},"references-count":19,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.23-0431","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,1]]}}}