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This randomized clinical trial compares the need for re-treatment of respiratory infection following hospitalization for community-acquired pneumonia among children receiving amoxicillin at high doses vs low doses and at 3-days vs 7-days duration. Question For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day noninferior to 70 to 90 mg/kg per day, and is a 3-day course noninferior to 7 days, with regard to the need for antibiotic re-treatment? Findings In this 2 x 2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic re-treatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin. Meaning Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day was noninferior to a dose of 70 to 90 mg/kg per day and 3 days was noninferior to 7 days with regard to the need for later antibiotic re-treatment. Importance The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants Multicenter, randomized, 2 x 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -infinity to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -infinity to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -infinity to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -infinity to 7.4%]; P value for interaction = .73). Conclusions and Relevance Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Improving maternal, newborn, and child health is a leading priority worldwide. It is a particularly urgent issue in South Sudan, which suffers from the world’s worst maternal mortality and among the worst newborn and child mortalities. A leading barrier to improving these health indices is limited frontline health worker capacity. In partnership with the Ministry of Health, the Division of Global Health and Human Rights (Department of Emergency Medicine, Massachusetts General Hospital, Boston, USA) has developed and is currently implementing its novel Maternal, Newborn, and Child Survival (MNCS) Initiative throughout much of South Sudan. The purpose of MNCS is to build frontline health worker capacity through a training package that includes:1. A participatory training course2. Pictorial checklists to guide prevention, care, and referral3. Re-useable medical equipment and commodities.Program implementation began in November 2010 utilizing a training-of-trainers model. To date, 72 local trainers and 632 frontline health workers have completed the training and received their MNCS checklists and commodities. Initial monitoring and evaluation results are encouraging as further evaluation continues. This innovative training package may also serve as a model for building capacity for maternal, newborn, and child health in other resource limited settings beyond South Sudan.