Antibiotics for acute watery or persistent with or without bloody diarrhoea in children: A systematic review and meta-analysis

Background: The use of antibiotics in the treatment of acute and persistent watery diarrhoea has long been a subject of contention. While the advantages of using antimicrobials are acknowledged, concerns remain regarding potential adverse effects and antibiotic resistance. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of antibiotics compared to placebos for the treatment of diarrhoea. Methods: We searched PubMed, CINAHL, the Cochrane Library, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Scopus from inception until 20 July 2023 for studies published after the year 2000 assessing antibiotics vs placebo in acute and persistent diarrhoea and/or blood in stools in children less than 10 years of age. We conducted a meta-analysis for the included studies, assessed them using the Risk of Bias 2 tool, and evaluated their quality of evidence through the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. This review was commissioned by WHO for revision of their guidelines for childhood diarrhoea management. Results: We included five randomised controlled trials (RCTs) for acute watery diarrhoea and no study for bloody diarrhoea. Our findings suggest that there is a significant increase in clinical cure (risk ratio (RR) = 2.28; 95% confidence interval (CI) = 1.52, 3.41; low certainty evidence) and parasitological cure (RR = 2.86; 95% CI = 1.72 to 4.74; low certainty evidence) among children with acute watery diarrhoea in the antibiotic group when compared to the placebo group. The duration of diarrhoea (in hours) was significantly reduced (mean difference = -24.90; 95% CI = -34.09, -15.71; low certainty evidence) in the intervention group, while the effect on all-cause mortality (RR = 0.71; 95% CI = 0.40, 1.27; moderate certainty evidence) and the need for intravenous fluid infusion (RR = 0.50; 95% CI = 0.05, 5.17; very low certainty evidence) were comparable between the two groups. Conclusions: In children under 10 years of age suffering from acute watery or persistent diarrhoea, antibiotics led to an apparent increase in cure rates. However, considering the low certainty of evidence, low number of studies with small sample sizes, and the fact that most studies were conducted in a single country, further investigation and cautious interpretation are warranted, as is a large multi-country RCT that would allow for firmer conclusions. Registration: PROSPERO: CRD42023447133.