Clinical Question

What is the optimal dosage of amoxicillin for managing community-acquired pneumonia (CAP) in children?

Bottom Line

In children with CAP who are discharged from an emergency department or inpatient setting within 48 hours, a lower dose of oral amoxicillin is noninferior to a higher dose, and three days of treatment is noninferior to seven days in reducing the need for antibiotic re-treatment. (Level of Evidence = 1b)

Synopsis

Although amoxicillin is widely recommended and used for the treatment of CAP in children, the optimal dose and treatment duration are uncertain. The investigators identified children six months and older with clinically diagnosed CAP (based on standard international guidelines) who were being discharged from the emergency department or inpatient ward within 48 hours of admission. Patients randomly received (concealed allocation assignment) one of four amoxicillin regimens: 35 to 50 mg per kg per day for three days; 35 to 50 mg per kg per day for seven days; 70 to 90 mg per kg per day for three days; or 70 to 90 mg per kg per day for seven days. Masking occurred by using matched active or placebo suspension for days 4 through 7. Individuals masked to treatment group assignment assessed the primary outcome of clinically indicated antibiotic re-treatment for respiratory tract infection within 28 days of randomization. The noninferiority margin was predetermined to be a conservative 8% difference in outcome rates. Complete follow-up data were available for 97% of participants at 28 days.

Using intention-to-treat analysis, the primary outcome occurred in 12.6% of children in the lower-dose groups vs. 12.4% in the higher-dose groups, and in 12.5% in the three-day treatment groups vs. 12.5% in the seven-day treatment groups. Both groups demonstrated noninferiority between dose and duration. In the subgroup of children with severe CAP, all groups demonstrated noninferiority.

This POEM aligns with Choosing Wisely Canada recommendations. The Choosing Wisely Canada Cold Standard toolkit provides tools for reducing unnecessary antibiotics.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Emergency department

Reference: Bielicki JA, Stöhr W, Barratt S, et al. PERUKI, GAPRUKI, and the CAP-IT Trial GroupEffect 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 [published correction appears in JAMA. 2021;326(21):2208]. JAMA. 2021;326(17):1713–1724.