Reference: JAMA Pediatr. 2021 Mar 8
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 five days of antibiotics are effective for community-acquired pneumonia (CAP) in adults – but what about kids? Current standard of care for treatment of CAP in children is 10 days of high-dose amoxicillin; however, data from the Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia (SAFER) trial suggest that five days may be adequate.
Researchers randomized 281 children aged 6 months to 10 years (median age 2.6 years) diagnosed with CAP in the ED who did not require hospitalization to five days of high-dose amoxicillin followed by either five days of high-dose amoxicillin with a different flavor (standard care) or five 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 fevered after day four of treatment were considered a clinical failure and received an additional five days of open-label amoxicillin. The primary outcome was clinical cure when measured at the 14- to 21-day appointment based on caregiver report and follow-up exam.
In per-protocol analysis, the more conservative and 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 14-21 days after enrollment (risk difference [RD] -0.016). While the point estimate of the difference in cure rates suggests five 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 actually excluded kids with missing data.
Given that up to 67% of CAP cases are thought to be viral, the Pediatric IDSA does not even 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 it is not as effective. Given that the difference in the clinical cure rates was sufficiently 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.
For more information, see the topic Antibiotics for Pediatric Outpatients with Community-acquired Pneumonia in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Nicole Jensen, MD, Faculty Development Fellow and Clinical Instructor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor of Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed; Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency; and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia.