Among children with acute watery diarrhea, the addition of azithromycin to standard World Health Organization (WHO) treatment protocols was not associated with a detectable survival benefit, according to results of a study published in JAMA Network Open.
Between July 2017 and July 2019, researchers performed a, randomized, double-blind clinical trial among high-risk children aged 2 to 23 months with acute nonbloody diarrhea in outpatient departments or community health centers in Bangladesh, India; Kenya, Malawi, Mali; Pakistan, and Tanzania (ClinicalTrials.gov, NCT03130114). Children were randomly assigned in a 1:1 fashion to receive either oral azithromycin (10 mg/kg) once daily for 3 days or placebo in addition to standard WHO treatment protocols. The follow-up duration was 180 days, and the primary outcomes were all-cause mortality up to 180 days and change in linear growth measured as change in the length-for-age z score between enrollment and day 90.
A total of 8266 children were included in the final analysis, of whom 4133 were in the azithromycin group and 4135 were in the placebo group. Of these patients, 54% were boys (n=4463) and the mean age was 11.6 (SD, 5.3) months. Among patients in both the azithromycin and placebo groups, 20 (0.5%) and 28 (0.7%) died, respectively (relative risk, 0.72; 95% CI, 0.40-1.27; P =.25). The mean change in length-for-age z score among patients in the azithromycin group was -0.16 (SD, 0.59) vs -0.19 (SD, 0.60) among those in the placebo group (risk difference, 0.03; 95%, CI 0.01-0.06; P =.007).
The researchers observed no differences between patients in either treatment group in regard to resistance shown by Escherichia coli or Streptococcus pneumonia isolates to other classes of antibiotics at any point within the follow-up period. Of note, the rate of hospitalization or death at day 10 was statistically significantly decreased among patients in the azithromycin group vs those in the placebo group (1.1% vs 1.6%).
This study was limited by its inability to demonstrate or exclude small differences in mortality associated with azithromycin due to the decreased mortality risk among patients in the placebo group. In addition, children with severe diarrheal disease or severe malnutrition were not included.
According to the researchers, “these results support rigorous adherence to the current WHO guidelines on the management of diarrhea and do not suggest that a change to global diarrhea management guidelines or policy is merited.”
Ahmed T, Chisti MJ, Rahman MW, et al. Effect of 3 days of oral azithromycin on young children with acute diarrhea in low-resource settings: A randomized clinical trial. JAMA Netw Open. 2021;4(12):e2136726. doi: 10.1001/jamanetworkopen.2021.36726