Evidence map›Paper›PMID 33176084›Full record

Trial reportThe New England journal of medicine2020

Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution.

Thuy Doan, Lee Worden, Armin Hinterwirth, Ahmed M Arzika, Ramatou Maliki, Amza Abdou, Lina Zhong, Cindi Chen, Catherine Cook, Elodie Lebas and 7 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 115 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02047981 phase4completednot on this map

Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Mortality Trial

TypeinterventionalSponsorUniversity of California, San FranciscoRan2014 to 2018Enrolled190,238ConditionsChildhood MortalityArmsAzithromycin, Placebo
NCT06358872 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Azithromycine Pour la Vie Des Enfants au Niger II

TypeinterventionalSponsorUniversity of California, San FranciscoRan2024 to 2028Enrolled3,300,000ConditionsMortality, Antimicrobial ResistanceArmsAzithromycin for Oral Suspension
3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Thuy DoanFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Lee WordenFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Armin HinterwirthFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Ahmed M ArzikaFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Ramatou MalikiFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Amza AbdouFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Lina ZhongFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Cindi ChenFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Catherine CookFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Elodie LebasFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Kieran S O'BrienFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Catherine E OldenburgFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Eric D ChowFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Travis C PorcoFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Marc LipsitchFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).ORCID 0000-0003-1504-9213
Jeremy D KeenanFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).
Thomas M LietmanFrom the Francis I. Proctor Foundation (T.D., L.W., A.H., L.Z., C. Chen, C. Cook, E.L., K.S.O., C.E.O., T.C.P., J.D.K., T.M.L.), the Departments of Ophthalmology (T.D., C.E.O., T.C.P., J.D.K., T.M.L.), Epidemiology and Biostatistics (C.E.O., T.C.P., T.M.L.), and Biochemistry and Biophysics (E.D.C.), and the Institute for Global Health Sciences (T.M.L.), University of California, San Francisco, San Francisco; the Carter Center (A.M.A., R.M.), the Ministry of Health (A.A.), and the Programme National de Santé Oculaire (A.A.), Niamey, Niger; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston (M.L.).

Funding

Ocular Surface Microbiome, Virome, and Pathogens in Ophthalmic Disease and HealthK08EY026986 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DOAN, THUY A · 2016 to 2020
$1.2M
NEI NIH HHS K08 EY026986
6 · The paper itself

Abstract

backgroundMass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.

methodsWe investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.

resultsOver the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.

conclusionsAmong villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).

Indexed as

Mass Drug AdministrationAnti-Bacterial AgentsAzithromycinChild MortalityChild, PreschoolDrug Resistance, BacterialFemaleGastrointestinal MicrobiomeHumansInfantMacrolidesMaleMetagenomeNigerSequence Analysis, DNAAnti-Bacterial AgentsAzithromycinMacrolides

Identifiers

PMID33176084
PMCPMC7492079

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.