Low-dose amoxicillin noninferior to higher dose for pediatric pneumonia
A lower dose of oral amoxicillin was noninferior to a higher dose in children with community-acquired pneumonia who were discharged from an ED or hospital ward, according to results of a 2x2 factorial, randomized clinical trial in JAMA.
The trial also showed that a shorter treatment duration was noninferior to a longer treatment duration.
“Few trials have compared different durations of the same antibiotic for treatment of community-acquired pneumonia (CAP) in adults or children, and none to our knowledge have compared both dose and duration in the same trial for childhood CAP,” Julia A. Bielicki, PhD, a researcher of pediatric infectious diseases in the Medical Research Council Clinical Trial Unit at University College London, and colleagues wrote.
Bielicki and colleagues enrolled 814 patients aged 6 months or older who were clinically diagnosed with CAP and received oral amoxicillin at discharge from an ED or inpatient center in the U.K. or Ireland between February 2017 and April 2019. The children were randomly assigned in a 1:1 ratio to receive either a lower dose of amoxicillin (35 mg/kg/d to 50 mg/kg/d) or a higher dose (70 mg/kg/d to 90 mg/kg/d) for 3 days or 7 days.
The researchers established a noninferiority margin of 8%. The primary outcome was clinically indicated antibiotic retreatment for a respiratory infection 28 days after randomization.
Antibiotic retreatment occurred within 28 days in 12.6% of patients who received a lower dose of amoxicillin compared with 12.4% of those who received a higher dose, according to Bielicki and colleagues. Also, retreatment occurred in 12.5% of patients in both the 3-day and 7-day treatment groups.
Although the shorter treatment duration was noninferior to the longer duration, the researchers found a significant difference between the two groups for cough duration, which persisted longer in the 3-day treatment group (12 days vs. 10 days; HR = 1.2; 90% CI, 1-1.4).
Among children with severe CAP, 17.3% in the low-dose group received retreatment compared with 13.5% in the high-dose group, as well as 16% in the shorter treatment group and 14.8% in the longer treatment group.
By the end of the study, 5% of children experienced a serious adverse event, 6% discontinued the trial medication early and 14% took fewer doses or a lower amount than prescribed.
“Among children with CAP discharged from an ED or hospital ward (within 48 hours), low-dose outpatient oral amoxicillin was noninferior to high dose, and 3-day duration was noninferior to 7 days, with regard to need for further antibiotic retreatment,” Bielicki and colleagues wrote. “However, disease severity, treatment setting, prior antibiotics, and acceptability of the noninferiority margin require consideration when interpreting the findings.”