Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children
Amy-Sarah Ginsburg1, Tisungane Mvalo1, Evangelyn Nkwopara1
1From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).
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.).
Insights
A 3-day amoxicillin treatment for childhood pneumonia in Malawi was found to be as effective as a 5-day course. This study provides evidence for shorter antibiotic durations in low-resource settings.
Area of Science:
- Pediatric infectious diseases
- Global health
- Antimicrobial stewardship
Background:
- Limited evidence exists on optimal antibiotic treatment durations for childhood pneumonia in African low-resource settings.
- Pneumonia remains a leading cause of child mortality globally, particularly in sub-Saharan Africa.
Purpose of the Study:
- To determine if a 3-day amoxicillin regimen is non-inferior to a 5-day regimen for treating chest-indrawing pneumonia in Malawian children.
- To inform antibiotic stewardship practices in resource-limited environments.
Main Methods:
- A double-blind, randomized, controlled, noninferiority trial was conducted with 3000 children (2-59 months) in Malawi.
- Participants received amoxicillin twice daily for either 3 or 5 days.
- Primary outcome was treatment failure by day 6; noninferiority defined as 3-day failure rate ≤ 1.5 times the 5-day rate.
Main Results:
- Treatment failure by day 6 occurred in 5.9% of the 3-day group vs. 5.2% of the 5-day group, meeting the noninferiority criterion.
- By day 14, treatment failure or relapse occurred in 12.5% of the 3-day group vs. 10.8% of the 5-day group.
- Serious adverse events were similar between the 3-day and 5-day treatment groups.
Conclusions:
- A 3-day course of amoxicillin is non-inferior to a 5-day course for treating chest-indrawing pneumonia in HIV-uninfected Malawian children.
- Shorter antibiotic durations may be a viable strategy for managing childhood pneumonia in similar settings.
- Findings support optimizing antibiotic use and potentially reducing treatment costs and side effects.
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