Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics

Patricia B. Pavlinac, James A. Platts-Mills, Jie Liu, Hannah E. Atlas, Jean Gratz, Darwin Operario, Elizabeth T. Rogawski McQuade, Dilruba Ahmed, Tahmeed Ahmed, Tahmina Alam, Per Ashorn, Henry Badji, Rajiv Bahl, Naor Bar-Zeev, Mohammod Jobayer Chisti, Jen Cornick, Aishwarya Chauhan, Ayesha De Costa, Saikat Deb, Usha DhingraQueen Dube, Christopher P. Duggan, Bridget Freyne, Wilson Gumbi, Aneeta Hotwani, Mamun Kabir, Ohedul Islam, Furqan Kabir, Irene Kasumba, Upendo Kibwana, Karen L. Kotloff, Shaila S. Khan, Victor Maiden, Karim Manji, Ashka Mehta, Latif Ndeketa, Ira Praharaj, Farah Naz Qamar, Sunil Sazawal, Jonathon Simon, Benson O. Singa, Sarah Somji, Samba O. Sow, Milagritos D. Tapia, Caroline Tigoi, Aliou Toure, Judd L. Walson, Mohammad Tahir Yousafzai, Eric R. Houpt

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background. Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. Methods. AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2–23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. Results. Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, −11.6 [95% confidence interval {CI}, −15.6 to −7.6]) and possible bacterial etiology (RDpossible, −8.7 [95% CI, −13.0 to −4.4]) but not in other children (RDunlikely, −0.3% [95% CI, −2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, −3.1 [95% CI, −5.3 to −1.0]; RDpossible, −2.3 [95% CI, −4.5 to −.01]; RDunlikely, −0.6 [95% CI, −1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. Conclusions. Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.

Original languageEnglish
Pages (from-to)988-998
Number of pages11
JournalJournal of Infectious Diseases
Volume229
Issue number4
DOIs
Publication statusPublished - 15 Apr 2024

Keywords

  • Shigella
  • azithromycin
  • bacterial diarrhea
  • molecular diagnostics
  • pediatric diarrhea

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