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Investigators from multiple institutions conducted a randomized trial to assess the effectiveness of different doses and lengths of treatment of amoxicillin in young children with community-acquired pneumonia (CAP). Participants were children >6 months old, weighing 6 to 24 kg, who were diagnosed with CAP and discharged from the emergency department (ED) or inpatient unit (after a hospitalization of <48 hours) at 1 of 28 centers in the UK or Ireland. Criteria for the diagnosis of CAP were based on British Thoracic Society guidelines. Patients who had received ß-lactam antibiotics for ≥48 hours were excluded, as were children with “complicated” pneumonia based on specific criteria. At enrollment, study participants were randomized using a 2x2 factorial design to low- (35-50 mg/kg/d) or high- (70-90 mg/kg/d) dose amoxicillin with a duration of treatment of 3 or 7 days.
The primary study outcome was treatment with another antibiotic for a respiratory infection within 28 days after enrollment. Kaplan-Meier methods were used to determine the proportion of children in each treatment group meeting this outcome. A priori it was determined that low-dose amoxicillin was non-inferior to high-dose, and/or 3-day treatment was non-inferior to 7 days, if the 1-sided 95% confidence interval (CI) of the difference in the proportion of children in each group treated with additional antibiotics was <8%. Secondary outcomes included parent- reported severity and duration of 9 CAP symptoms in their child; differences between groups were assessed.
A total of 824 children were enrolled, and 814 received at least 1 dose of trial medication. The median age of these children was 2.5 years. At enrollment, 54% were febrile and 65% were tachypneic; 591 (73%) patients were discharged from the ED and 223 (27%) from an in-patient unit. Data on the primary outcome were available on 789 participants. Overall, 12.5% of study children received additional antibiotics for a respiratory infection within 28 days. There were no differences between those in the low- or high-dose amoxicillin group who received additional antibiotics (12.6% and 12.4%, respectively; difference, 0.2%; 95% CI, -∞, 4.0) or between those treated for 3 or 7 days (12.5% and 12.5%, respectively; difference, 0.1%; 95% CI, -∞, 3.9%), thus the criterion for non-inferiority were met for both low-dose amoxicillin and 3 days of treatment. There also were no significant differences reported in severity or duration of most CAP symptoms. However, cough duration was significantly longer in children treated with 3 days of amoxicillin than in those treated for 7 days (median 12 days vs 10 days, P = 0.04).
The authors conclude that low-dose amoxicillin was non-inferior to high-dose and treatment for 3 days non-inferior to 7 days of treatment in young children with CAP.
Dr Doolittle...
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