Original Investigation November 2, 2021<\/p>\n\n\n\n
Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial<\/h1>\n\n\n\n
Julia A.\u00a0Bielicki,\u00a0Wolfgang\u00a0St\u00f6hr,\u00a0Sam\u00a0Barratt,\u00a0et al<\/h3>\n\n\n\n
Importance<\/strong> The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.<\/p>\n\n\n\n
Objective<\/strong> To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong> Multicenter, randomized, 2\u2009\u00d7\u20092 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.<\/p>\n\n\n\n
Interventions<\/strong> Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg\/kg\/d; n\u2009=\u2009410) or higher dose (70-90 mg\/kg\/d; n\u2009=\u2009404), for a shorter duration (3 days; n\u2009=\u2009413) or a longer duration (7 days; n\u2009=\u2009401).<\/p>\n\n\n\n
Main Outcomes and Measures<\/strong> 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<\/em> isolates.<\/p>\n\n\n\n
Results<\/strong> 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 \u2013\u221e 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 \u2013\u221e to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P<\/em>\u2009=\u2009.63). 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<\/em>\u2009=\u2009.04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P<\/em>\u2009=\u2009.03). 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, \u2013\u221e to10%]; P<\/em> value for interaction\u2009=\u2009.18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, \u2013\u221e to 7.4%]; P<\/em> value for interaction\u2009=\u2009.73).<\/p>\n\n\n\n<\/figure>\n\n\n\n
Conclusions and Relevance<\/strong> 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.<\/p>\n\n\n\n
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