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Randomized Controlled Trial
. 2024 Apr 12;229(4):988-998.
doi: 10.1093/infdis/jiad252.

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

Patricia B Pavlinac  1   2 , James A Platts-Mills  3 , Jie Liu  4 , Hannah E Atlas  1 , Jean Gratz  3 , Darwin Operario  3 , Elizabeth T Rogawski McQuade  5 , Dilruba Ahmed  6 , Tahmeed Ahmed  7 , Tahmina Alam  7 , Per Ashorn  8 , Henry Badji  9 , Rajiv Bahl  10 , Naor Bar-Zeev  11 , Mohammod Jobayer Chisti  7 , Jen Cornick  12 , Aishwarya Chauhan  13 , Ayesha De Costa  10 , Saikat Deb  13 , Usha Dhingra  13 , Queen Dube  14 , Christopher P Duggan  15 , Bridget Freyne  12   16   17 , Wilson Gumbi  18 , Aneeta Hotwani  19 , Mamun Kabir  7 , Ohedul Islam  7 , Furqan Kabir  19 , Irene Kasumba  20 , Upendo Kibwana  21 , Karen L Kotloff  20   22 , Shaila S Khan  7 , Victor Maiden  12 , Karim Manji  21 , Ashka Mehta  20 , Latif Ndeketa  12 , Ira Praharaj  23 , Farah Naz Qamar  19 , Sunil Sazawal  13 , Jonathon Simon  10 , Benson O Singa  24 , Sarah Somji  21 , Samba O Sow  9 , Milagritos D Tapia  20 , Caroline Tigoi  18 , Aliou Toure  9 , Judd L Walson  1   2   25 , Mohammad Tahir Yousafzai  18 , Eric R Houpt  3 ; AntiBiotics for Children with severe Diarrhea (ABCD) Study Group
Collaborators, Affiliations
Randomized Controlled Trial

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

Patricia B Pavlinac et al. J Infect Dis. .

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.

Clinical trials registration: NCT03130114.

Keywords: Shigella; azithromycin; bacterial diarrhea; molecular diagnostics; pediatric diarrhea.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Participant flowchart describing children included in the subanalysis of diarrhea etiology among children enrolled in the AntiBiotics for Children with severe Diarrhea (ABCD) trial. Abbreviations: ABCD, AntiBiotics for Children with severe Diarrhea; EPEC, enteropathogenic Escherichia coli; qPCR, quantitative polymerase chain reaction; ST-ETEC, enterotoxigenic Escherichia coli encoding heat-stable toxin.
Figure 2.
Figure 2.
Likely etiologies (determined by pathogen-specific diarrhea-attribution cycle threshold cutoffs) among AntiBiotics for Children with severe Diarrhea (ABCD) study participants by site and age. Showing etiologies with 10% prevalence or more. Abbreviations: EPEC, enteropathogenic Escherichia coli; ST-ETEC, enterotoxigenic Escherichia coli encoding heat-stable toxin.
See this image and copyright information in PMC

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