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

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 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.