In a study recently published in JAMA, findings revealed that a lower dose of oral amoxicillin was noninferior to a higher dose in children with community-acquired pneumonia (CAP) who were discharged from an emergency department (ED) or hospital ward. The trial also revealed that a shorter treatment duration was noninferior to a longer treatment duration.
The researchers conducted a multicenter, randomized, 2 × 2 factorial noninferiority trial that enrolled 824 children aged 6 months and older with clinically diagnosed CAP. Patients were treated with amoxicillin upon discharge from EDs and inpatient wards of 28 hospitals in the UK and one in Ireland between February 2017 and April 2019, with the last trial visit on May 21, 2019. In the trial, pediatric patients 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).
The researchers established a noninferiority margin of 8%. The primary outcome was clinically indicated antibiotic retreatment for a respiratory infection 28 days after randomization. Secondary outcomes included severity/duration of nine parent-reported CAP symptoms, three antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.
Of 824 participants randomized into one of the four groups, 814 received at least one 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 versus higher dosing, the primary outcome occurred in 12.6% of subjects with the lower dose versus 12.4% of those with the higher dose (difference, 0.2% [1-sided 95% CI –∞to 4.0%]), and in 12.5% of those with 3-day treatment versus 12.5% of those with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ 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 versus 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 versus 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to 10%]; P value for interaction = .18) and in 16.0% with 3-day treatment versus 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞to 7.4%]; P value for interaction = .73).
The authors concluded that among pediatric patients with CAP discharged from an ED 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 retreatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin necessitate consideration when interpreting the findings.
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