Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children

Abstract

Background: Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking.

Methods: We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14.

Results: From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group).

Conclusions: In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.).

Figure 1

Consort diagram by treatment group ¹Children may be ineligible for more than one reason. ²Missing follow-up data may be due to missed visits or visits occurring outside visit windows. ³Missing follow-up data n’s do not add up because some children had missing follow-up data for either Day 2 or Day 4 or both, but had outcome data available for Day 6.