Is a shorter course of antibiotics better for children with CAP?

Abstract

Results of the SCOUT-CAP randomized clinical trial published in the January 2022 issue of JAMA Pediatrics found that a short 5-day antibiotic treatment course is superior to a standard 10-day regimen for children with non-severe community-acquired pneumonia (CAP) in an outpatient setting. A short 5-day strategy reduced both antibiotic exposure and resistance while presenting a similar clinical response and antibiotic-related adverse effect profile as a standard 10-day course. According to the study, CAP is one of the most common serious infections in pediatric populations, with reports of about 1.5 million ambulatory visits by U.S. children yearly. “It’s critical that we minimize the use of unnecessary antibiotics, both to eliminate the risk of antibiotic adverse effects and slow the progression of antimicrobial resistance, a global public health threat,” said Derek Williams, MD, MPH, lead investigator of the study. Although antibiotics are not always needed, when required it is important to choose the right antibiotic, at the right dose, and only for as long as necessary to effectively treat the infection, said Williams, who is an associate professor of pediatrics at Vanderbilt University School of Medicine. The randomized, double-blind, placebo-controlled clinical trial included 380 healthy children between the ages of 6 months and roughly 6 years with non-severe CAP in 8 U.S. cities between December 2016 and December 2019. They were seen in outpatient clinics, urgent care settings, and emergency departments. Children were only included in the study if they had not experienced the following at time of enrollment based on caregiver reporting: subjective fever or temperature 38.3°C or higher in the previous 24 hours; tachypnea (50 and 40 breaths per minute for children younger than 2 years, and 2 years and older, respectively); and severe cough. Study participants were randomized 1:1 to either receive a 5-day course of matching placebo or an additional 5-day course of the originally prescribed β-lactam antibiotic—including amoxicillin, amoxicillin and clavulanate, or cefdinir—on day 6 of therapy. Dosing for amoxicillin or amoxicillin and clavulanate was 80 to 100 mg/kg a day (maximum 2,000 mg a day) based on the amoxicillin component divided twice daily, and cefdinir dosing was 12 to 16 mg/kg a day (maximum 600 mg a day) divided twice daily. The taste and appearance of the matching placebo was consistent and dosed at the same interval as the original 5-day course therapy. Study participants underwent two in-person outcome assessment visits on study days 6 to 10 and days 19 to 25, respectively. The primary composite endpoint—a ranking of each child’s clinical response, symptom resolution, and antibiotic-associated adverse effects—made up the end-of-treatment response adjusted for duration of antibiotic risk (RADAR) in an ordinal desirability of outcome ranking (DOOR). Participants were then ranked by the number of antibiotic days within each DOOR, with the hypothesis that shorter antibiotic durations were more desirable. RADAR was used to determine the more desirable outcome probability estimate for short- versus standard-course strategy. During the antibiotic resistance analysis, throat swab samples were taken from the oropharyngeal flora of 171 children between days 19 and 25 to assess antibiotic resistance. The research findings showed that a majority of children had an adequate clinical response to both strategies, with fewer than 10% of children experiencing a poor response. The research team found that the short-course strategy had a 69% probability of a more desirable RADAR outcome compared with the standard-course strategy. The antibiotic resistance analysis showed that the range of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC and β-lactamase RGPC, according to the study. “SCOUT-CAP is the first clinical trial to use this innovative trial design, taking into account both the response to and potential side effects of antibiotic therapy,” said C. Buddy Creech, MD, MPH, a professor of pediatrics at Vanderbilt University Medical Center, who was also part of the study. “These data are immediately applicable to frontline clinicians, and we hope it helps to shift the paradigm for childhood pneumonia toward more judicious treatment approaches, resulting in safer and more effective care,” said Williams. Future trials using this approach may allow us to optimize therapy for other infectious diseases in children and adults, said Creech.