As antibiotic-resistant infections rise, antibiotic stewardship becomes increasingly crucial. For many infections, evidence has demonstrated that shorter courses of antibiotics are equally as effective as longer ones. For example, we know that 5 days of antibiotics is effective for community-acquired pneumonia (CAP) in adults — but what about kids? Currently, it is common to treat CAP in children with 10 days of high-dose amoxicillin; however, data from the Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia (SAFER) trial suggest that 5 days may be adequate.

Researchers randomized 281 children aged 6 months to 10 years (median age 2.6 years) diagnosed with CAP in an emergency department setting who did not require hospitalization to 5 days of high-dose amoxicillin followed by either an additional 5 days of high-dose amoxicillin with a different flavor (standard care) or 5 days of placebo (intervention group).

Caregivers were asked to record daily temperatures, respiratory symptoms, adverse reactions, missed doses, and absences from school, daycare, or caregiver employment. Telephone follow-up occurred twice in the first 10 days, at day 30, and in-person once between days 14 and 21. Patients in the intervention group who had a fever after day 4 of treatment were considered a clinical failure and received an additional 5 days of open-label amoxicillin. The primary outcome was clinical cure measured at the 14- to 21-day appointment based on caregiver report and follow-up examination.

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In the per-protocol analysis, the preferred approach for noninferiority trials, short-course amoxicillin did not meet criteria for noninferiority at the prespecified margin of 7.5%. In the intervention group, 101 of 114 patients (88.6%) compared with 99 of 109 patients (90.8%) in the control group reported clinical cure at 14 to 21 days after enrollment (risk difference [RD] -0.016). While the point estimate of the difference in cure rates suggests 5 days of treatment is only slightly worse with a 1.6% reduction in cure, the limit of the confidence interval is 8.7%, which surpasses the noninferiority margin of 7.5%. The same goes for the “strict” per-protocol analysis, which included only children with radiologically-confirmed pneumonia. Noninferiority was met in what the authors reported was an intention-to-treat analysis, although the analysis excluded kids with missing data.

Given that up to 67% of CAP cases are thought to be viral, the Pediatric Infectious Diseases Society and Infectious Diseases Society of America guidelines do not recommend antibiotics for CAP in preschool-aged children. When antibiotics are used, shorter treatment durations are generally preferred as they have the potential to reduce antibiotic resistance, adverse events, and cost. While a 5-day course of amoxicillin was not proven to be noninferior by the results of this trial, it would be wrong to conclude that this means it is not as effective. Given that the difference in the clinical cure rates was quite small, a larger trial with better follow-up might demonstrate similar efficacy to a 10-day course.

All in all, a 5-day antibiotic course could be considered for children with uncomplicated CAP in the outpatient setting and close follow-up.

Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Massachusetts, and assistant clinical professor in family medicine, University of Massachusetts Medical School, Worcester.

DynaMed is a database that provides evidence-based information on more than 3000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.


Pernica JM, Harman S, Kam AJ, et al. Short-course antimicrobial therapy for pediatric community-acquired pneumonia: the SAFER randomized clinical trial. JAMA Pediatr. 2021;175(5):475-482. doi:10.1001/jamapediatrics.2020.6735