1. In this study, adding azithromycin to standard management of acute diarrhea in children lowered risk of hospitalization and reduced change-in-weight at 90-days post treatment.

2. Adding azithromycin to standard management for acute childhood diarrhea did not improve 180-day mortality.

Evidence Rating Level: 1 (Excellent)

The current WHO guidelines do not recommend routine use of antibiotics in treating children with acute watery diarrhea. However, given that a significant proportion of acute watery diarrhea in the low-and-middle income settings could be caused by bacterial infection, addition of antibiotics to standard of care for watery diarrhea in dehydrated or undernourished children may help reduce mortality and improve growth.

This randomized control trial examined the efficacy of antibiotic azithromycin addition to standardized care in 8266 children (54% male) aged 2 to 23 months with acute watery diarrhea, dehydration, and/or moderate wasting (decrease weight-for-length). Children were recruited from 2017-2019 and were from 36 outpatient hospitals or community health centers in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Children were excluded if they had dysentery, suspected cholera, severe acute malnutrition, signs of other infections requiring antibiotics, and antibiotic use in last 14 days. Enrolled children were randomly assigned to either receive 10mg/kg oral azithromycin or placebo once daily for 3 days in addition to WHO standard care protocols for management of watery diarrhea. Each child was followed for 180 days. The primary outcome examined were changes in growth 90-days after enrollment and all-cause mortality up to 180 days after enrollment.

Results demonstrated there was a 21% lower risk of hospitalization or death in the 90-day period after azithromycin treatment and a smaller decrease in length-for-age in antibiotic group (-0.16) compared to control group (-0.19). However, at 180 days, the change in mortality was not significantly different between antibiotic (0.5%) and control group (0.7%). However, this study was limited in that it could neither demonstrate or exclude the possibility of a difference in mortality between the two groups considering the small risk of mortaltity in the control group (which would require a much larger sample size). Therefore, although the results of this study suggest continued adherence to current WHO protocols for acute watery diarrhea, future studies with more patients and assessment of additional outcomes may identify specific populations or circumstances in which antibiotic use could be helpful.

Click to read the study in JAMA Network Open

Image: PD

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