Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial

Gabrielle B. McCallum; Siew M. Fong; Keith Grimwood; Anna M. Nathan; Catherine A. Byrnes; Mong H. Ooi; Nachal Nachiappan; Noorazlina Saari; Peter S. Morris; Tsin W. Yeo; Robert S. Ware; Blueren W. Elogius; Victor M. Oguoma; Stephanie T. Yerkovich; Jessie de Bruyne; Katrina A. Lawrence; Bilawara Lee; John W. Upham; Paul J. Torzillo; Anne B. Chang

doi:10.1097/INF.0000000000003558

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial

Gabrielle B. McCallum, Siew M. Fong, Keith Grimwood, Anna M. Nathan, Catherine A. Byrnes, Mong H. Ooi, Nachal Nachiappan, Noorazlina Saari, Peter S. Morris, Tsin W. Yeo, Robert S. Ware, Blueren W. Elogius, Victor M. Oguoma, Stephanie T. Yerkovich, Jessie de Bruyne, Katrina A. Lawrence, Bilawara Lee, John W. Upham, Paul J. Torzillo, Anne B. Chang

Child and Maternal Health

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	549-555
Number of pages	7
Journal	The Pediatric Infectious Disease Journal
Volume	41
Issue number	7
DOIs	https://doi.org/10.1097/INF.0000000000003558
Publication status	Published - 1 Jul 2022

Bibliographical note

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.

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Dive into the research topics of 'Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial'. Together they form a unique fingerprint.

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McCallum, G. B., Fong, S. M., Grimwood, K., Nathan, A. M., Byrnes, C. A., Ooi, M. H., Nachiappan, N., Saari, N., Morris, P. S., Yeo, T. W., Ware, R. S., Elogius, B. W., Oguoma, V. M., Yerkovich, S. T., de Bruyne, J., Lawrence, K. A., Lee, B., Upham, J. W., Torzillo, P. J., & Chang, A. B. (2022). Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial. The Pediatric Infectious Disease Journal, 41(7), 549-555. https://doi.org/10.1097/INF.0000000000003558

McCallum, Gabrielle B. ; Fong, Siew M. ; Grimwood, Keith et al. / Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings : Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial. In: The Pediatric Infectious Disease Journal. 2022 ; Vol. 41, No. 7. pp. 549-555.

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title = "Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial",

abstract = "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.",

keywords = "amoxicillin-clavulanate, placebo, pneumonia, randomized controlled trial, children",

author = "McCallum, {Gabrielle B.} and Fong, {Siew M.} and Keith Grimwood and Nathan, {Anna M.} and Byrnes, {Catherine A.} and Ooi, {Mong H.} and Nachal Nachiappan and Noorazlina Saari and Morris, {Peter S.} and Yeo, {Tsin W.} and Ware, {Robert S.} and Elogius, {Blueren W.} and Oguoma, {Victor M.} and Yerkovich, {Stephanie T.} and {de Bruyne}, Jessie and Lawrence, {Katrina A.} and Bilawara Lee and Upham, {John W.} and Torzillo, {Paul J.} and Chang, {Anne B.}",

note = "Funding Information: A.B.C. is supported by a National Health and Medical Research Council practitioner fellowship (number 1154302) and Children{\textquoteright}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 {\textcopyright} 2022 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2022",

month = jul,

day = "1",

doi = "10.1097/INF.0000000000003558",

language = "English",

volume = "41",

pages = "549--555",

journal = "The Pediatric Infectious Disease Journal",

issn = "0891-3668",

publisher = "Lippincott Williams & Wilkins",

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McCallum, GB, Fong, SM, Grimwood, K, Nathan, AM, Byrnes, CA, Ooi, MH, Nachiappan, N, Saari, N, Morris, PS , Yeo, TW, Ware, RS, Elogius, BW, Oguoma, VM, Yerkovich, ST, de Bruyne, J, Lawrence, KA, Lee, B, Upham, JW, Torzillo, PJ & Chang, AB 2022, 'Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial', The Pediatric Infectious Disease Journal, vol. 41, no. 7, pp. 549-555. https://doi.org/10.1097/INF.0000000000003558

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial. / McCallum, Gabrielle B.; Fong, Siew M.; Grimwood, Keith et al.
In: The Pediatric Infectious Disease Journal, Vol. 41, No. 7, 01.07.2022, p. 549-555.

Research output: Contribution to journal › Article › peer-review

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

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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 -

McCallum GB, Fong SM, Grimwood K, Nathan AM, Byrnes CA, Ooi MH et al. Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial. The Pediatric Infectious Disease Journal. 2022 Jul 1;41(7):549-555. doi: 10.1097/INF.0000000000003558

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial

Abstract

Bibliographical note

UN SDGs

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