Azithromycin for bacterial watery diarrhea: A reanalysis of the AntiBiotics for Children with severe Diarrhea (ABCD) trial incorporating molecular diagnostics

Pavlinac PB, Platts-Mills J, Liu J, Atlas HE, Gratz J, Operario D, Rogawski McQuade E, Ahmed D, Ahmed T, Alam T, Ashorn P, Badji H, Bahl R, Bar-Zeev N, Chisti MJ, Cornick J, Chauhan A, De Costa A, Deb S, Dhingra U, Dube Q, Duggan CP, Freyne B, Gumbi W, Hotwani A, Kabir M, Islam O, Kabir F, Kasumba I, Kibwana U, Kotloff KL, Khan SS, Maiden V, Manji K, Mehta A, Ndeketa L, Praharaj I, Qamar FN, Sazawal S, Simon J, Singa BO, Somji S, Sow SO, Tapia MD, Tigoi C, Toure A, Walson JL, Tahir Yousafzai M, Houpt ER
J Infect Dis. 2023;

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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 PCR 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 6,692 children, the leading likely etiologies were rotavirus(21.1%), ST-ETEC(13.3%), Shigella(12.6%) and Cryptosporidium(9.6%). More than one quarter (1894[28.3%]) had a likely and 1,153(17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin vs. placebo among children with a likely bacterial etiology (Risk Difference[RD]likely: -11.6[95%CI:-15.6, -7.6] and possible bacterial etiology (RDpossible:-8.7 [95%CI:-13.0, -4.4]) but not in other children (RDunlikely:-0.3%[95%CI:-2.9%,2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely:-3.1[95%CI:-5.3, -1.0], RDpossible: -2.3[95%CI: -4.5, -0.01], and (RDunlikely:-0.6 [95%CI:-1.9,0.6]). The magnitude of risk differences were similar among specific likely bacterial etiologies, including Shigella. CONCLUSION: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.