Amoxicillin 3 vs 5 days for chest-indrawing pneumonia in Malawian children

BACKGROUND: Evidence supporting duration of antibiotic treatment for children in low-resource African settings with chest-indrawing pneumonia is lacking. METHODS: We conducted a double-blind, randomized controlled 2-arm, non-inferiority trial in Lilongwe, Malawi with follow-up for 14 days to determine whether treatment with 3 days of amoxicillin for chest-indrawing pneumonia is less effective than 5 days. HIV-uninfected children aged 2 to 59 months with chest-indrawing pneumonia were randomized to 3-or 5-day amoxicillin twice-daily. Primary endpoint was the proportion of children with treatment failure (TF) by Day 6 with a relative non-inferiority margin of 1.5 times the TF rate in the 5-day amoxicillin group. Planned secondary analyses included TF or relapse by Day 14. RESULTS: Between March 29, 2016 and April 1, 2019, 3000 children were randomly assigned to 3-day (n=1497) or 5-day (n=1503) amoxicillin. Children receiving 3-day had a 5.9% (85/1442 with outcome data) TF rate by Day 6, within the non-inferiority margin of those receiving 5-day (5.2% (75/1456) TF rate), with an adjusted absolute difference of 0.75% and 95% confidence interval (CI) -0.92%,2.41%. Among children with known Day 14 outcome, 176/1411 (12.5%) receiving 3-day and 154/1429 (10.8%) receiving 5-day had TF by Day 6 or relapse by Day 14 (absolute difference 1.7%, 95%CI -0.7%,4.1%). There were no unexpected serious adverse events. CONCLUSIONS: In HIV-uninfected African children, 3 days of amoxicillin treatment for chestindrawing pneumonia was non-inferior to 5 days. We recommend revisiting antibiotictreatment guidelines applicable to similar pediatric populations. ClinicalTrials.gov registration: NCT02760420.