TY - JOUR
T1 - Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings
T2 - Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial
AU - McCallum, Gabrielle B.
AU - Fong, Siew M.
AU - Grimwood, Keith
AU - Nathan, Anna M.
AU - Byrnes, Catherine A.
AU - Ooi, Mong H.
AU - Nachiappan, Nachal
AU - Saari, Noorazlina
AU - Morris, Peter S.
AU - Yeo, Tsin W.
AU - Ware, Robert S.
AU - Elogius, Blueren W.
AU - Oguoma, Victor M.
AU - Yerkovich, Stephanie T.
AU - de Bruyne, Jessie
AU - Lawrence, Katrina A.
AU - Lee, Bilawara
AU - Upham, John W.
AU - Torzillo, Paul J.
AU - Chang, Anne B.
N1 - Funding Information:
A.B.C. is supported by a National Health and Medical Research Council practitioner fellowship (number 1154302) and Children’s Hospital Foundation Queensland (Grant 50286). The other authors have no conflicts of interest to disclose.
Funding Information:
The study was funded by the Australian National Health and Medical Research Council (NHMRC) project grant (number 1098443) and supported by a NHMRC Center for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (grant number 1040830). The New Zealand site was supported by a 2-year grant from CureKids, New Zealand (grant 3571). The Kuala Lumpur site was partially funded by a Malaysian Health grant RP026-14HTM.
Publisher Copyright:
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - BACKGROUND: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP. METHODS: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks. RESULTS: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance. CONCLUSIONS: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits.
AB - BACKGROUND: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP. METHODS: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks. RESULTS: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance. CONCLUSIONS: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits.
KW - amoxicillin-clavulanate
KW - placebo
KW - pneumonia
KW - randomized controlled trial
KW - children
UR - http://www.scopus.com/inward/record.url?scp=85131770544&partnerID=8YFLogxK
U2 - 10.1097/INF.0000000000003558
DO - 10.1097/INF.0000000000003558
M3 - Article
C2 - 35476706
AN - SCOPUS:85131770544
SN - 0891-3668
VL - 41
SP - 549
EP - 555
JO - The Pediatric Infectious Disease Journal
JF - The Pediatric Infectious Disease Journal
IS - 7
ER -