Effect of 3 Days of Oral Azithromycin on Young Children with Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial

Tahmeed Ahmed, Mohammod Jobayer Chisti, Muhammad Waliur Rahman, Tahmina Alam, Dilruba Ahmed, Irin Parvin, Md Farhad Kabir, Sunil Sazawal, Pratibha Dhingra, Arup Dutta, Saikat Deb, Aishwarya Chouhan, Anil Kumar Sharma, Vijay Kumar Jaiswal, Usha Dhingra, Judd L. Walson, Benson O. Singa, Patricia B. Pavlinac, Christine J. McGrath, Churchil NyabindaEmily L. Deichsel, Maurine Anyango, Kevin Mwangi Kariuki, Doreen Rwigi, Stephanie N. Tornberg-Belanger, Karen L. Kotloff, Samba O. Sow, Milagritos D. Tapia, Fadima Cheick Haidara, Ashka Mehta, Flanon Coulibaly, Henry Badji, Jasnehta Permala-Booth, Sharon M. Tennant, Dramane Malle, Naor Bar-Zeev, Queen Dube, Bridget Freyne, Nigel Cunliffe, Latif Ndeketa, Desiree Witte, Chifundo Ndamala, Jennifer Cornick, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shahida Qureshi, Sadia Shakoor, Rozina Thobani, Aneeta Hotwani, Furqan Kabir, Jan Mohammed, Karim Manji, Christopher P. Duggan, Rodrick Kisenge, Christopher R. Sudfeld, Upendo Kibwana, Sarah Somji, Mohamed Bakari, Cecylia Msemwa, Abraham Samma, Rajiv Bahl, Ayesha De Costa, Jonathon Simon, Per Ashorn

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

Original languageEnglish
Article numbere2136726
JournalJAMA network open
Issue number12
Publication statusPublished - 16 Dec 2021


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