Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial.

Abstract

Importance

Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance.

Objective

To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children.

Design, setting, and participants

Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020.

Intervention

On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic.

Main outcomes and measures

The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora.

Results

A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number 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 (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and β-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03).

Conclusions and relevance

In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance.

Trial registration

ClinicalTrials.gov Identifier: NCT02891915.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1001/jamapediatrics.2021.5547

Publication Info

Williams, Derek J, C Buddy Creech, Emmanuel B Walter, Judith M Martin, Jeffrey S Gerber, Jason G Newland, Lee Howard, Meghan E Hofto, et al. (2022). Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial. JAMA pediatrics. 10.1001/jamapediatrics.2021.5547 Retrieved from https://hdl.handle.net/10161/24319.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Walter

Emmanuel Benjamin Walter

Professor of Pediatrics

Dr. Emmanuel Walter, MD, MPH, Professor of Pediatrics, serves as the Duke Human Vaccine Institute (DHVI) Chief Medical Officer and directs the Duke Vaccine and Trials Unit. In these roles, Dr. Walter provides strategic and operational leadership for clinical research conducted at the Institute.  In addition, he provides oversight of regulatory compliance for DHVI clinical research activities.

Dr. Walter has dedicated his career to advancing research and clinical practice in vaccinology, infectious diseases, and child health. He currently serves as the principal investigator for the Duke Clinical Core of the Collaborative Influenza Vaccine Innovations Centers (CIVICs) funded by the National Institute of Allergy and Infectious Diseases (NIAID).  The goal of this work is to evaluate promising next generation influenza vaccine candidates in Phase I and Phase I/II clinical trials and human challenge studies.  He is also the Duke Principal Investigator for the CDC-funded Clinical Immunization Safety Assessment Project which conducts studies to identify risk factors and preventive strategies for adverse events following immunization, particularly in special populations. Lastly, he is the Principal Investigator for the  CDC-funded coordinating center of the influenza and other respiratory virus vaccine effectiveness network.  This work provides national estimates for influenza and other respiratory virus vaccine effectiveness in persons presenting with respiratory illness in the ambulatory setting.

Dr. Walter's focused area of interest include vaccine development, vaccine safety, vacc9je effectiveness, vaccine coverage, prevention and treatment of infectious diseases.


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