Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT

Background: Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children. Objectives: To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sam Barratt, Julia A Bielicki, David Dunn, Saul N Faust, Adam Finn, Lynda Harper, Pauline Jackson, Mark D Lyttle, Colin VE Powell, Louise Rogers, Damian Roland, Wolfgang Stöhr, Kate Sturgeon, Elia Vitale, Mandy Wan, Diana M Gibb, Mike Sharland
Formato:	article
Lenguaje:	EN
Publicado:	NIHR Journals Library 2021
Materias:	community-acquired pneumonia children amoxicillin antibiotic treatment/duration antibiotic treatment/dose randomised controlled trial Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/0e90f12c77e941da9612c5c56c0edb52
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0e90f12c77e941da9612c5c56c0edb52
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	community-acquired pneumonia children amoxicillin antibiotic treatment/duration antibiotic treatment/dose randomised controlled trial Medical technology R855-855.5
spellingShingle	community-acquired pneumonia children amoxicillin antibiotic treatment/duration antibiotic treatment/dose randomised controlled trial Medical technology R855-855.5 Sam Barratt Julia A Bielicki David Dunn Saul N Faust Adam Finn Lynda Harper Pauline Jackson Mark D Lyttle Colin VE Powell Louise Rogers Damian Roland Wolfgang Stöhr Kate Sturgeon Elia Vitale Mandy Wan Diana M Gibb Mike Sharland Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
description	Background: Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children. Objectives: To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a lower and a higher dose at hospital discharge in children with uncomplicated community-acquired pneumonia. Design: A multicentre randomised double-blind 2 × 2 factorial non-inferiority trial in secondary care in the UK and Ireland. Setting: Paediatric emergency departments, paediatric assessment/observation units and inpatient wards. Participants: Children aged > 6 months, weighing 6–24 kg, with a clinical diagnosis of community-acquired pneumonia, in whom treatment with amoxicillin as the sole antibiotic was planned on discharge. Interventions: Oral amoxicillin syrup at a dose of 35–50 mg/kg/day compared with a dose of 70–90 mg/kg/day, and 3 compared with 7 days’ duration. Children were randomised simultaneously to each of the two factorial arms in a 1 : 1 ratio. Main outcome measures: The primary outcome was clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Secondary outcomes included severity and duration of parent/guardian-reported community-acquired pneumonia symptoms, drug-related adverse events (including thrush, skin rashes and diarrhoea), antimicrobial resistance and adherence to trial medication. Results: A total of 824 children were recruited from 29 hospitals. Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6–2.7) years; 52% male] were randomised to either 3 (n = 413) or 7 days (n = 401) of trial medication at either lower (n = 410) or higher (n = 404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval –3.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval –3.7% to 4.0%), both demonstrating non-inferiority. Resolution of cough was faster in the 7-day arm than in the 3-day arm for cough (10 days vs. 12 days) (p = 0.040), with no difference in time to resolution of other symptoms. The type and frequency of adverse events and rate of colonisation by penicillin-non-susceptible pneumococci were comparable between arms. Limitations: End-of-treatment swabs were not taken, and 28-day swabs were collected in only 53% of children. We focused on phenotypic penicillin resistance testing in pneumococci in the nasopharynx, which does not describe the global impact on the microflora. Although 21% of children did not attend the final 28-day visit, we obtained data from general practitioners for the primary end point on all but 3% of children. Conclusions: Antibiotic retreatment, adverse events and nasopharyngeal colonisation by penicillin-non-susceptible pneumococci were similar with the higher and lower amoxicillin doses and the 3- and 7-day treatments. Time to resolution of cough and sleep disturbance was slightly longer in children taking 3 days’ amoxicillin, but time to resolution of all other symptoms was similar in both arms. Future work: Antimicrobial resistance genotypic studies are ongoing, including whole-genome sequencing and shotgun metagenomics, to fully characterise the effect of amoxicillin dose and duration on antimicrobial resistance. The analysis of a randomised substudy comparing parental electronic and paper diary entry is also ongoing. Trial registration: Current Controlled Trials ISRCTN76888927, EudraCT 2016-000809-36 and CTA 00316/0246/001-0006. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 60. See the NIHR Journals Library website for further project information.
format	article
author	Sam Barratt Julia A Bielicki David Dunn Saul N Faust Adam Finn Lynda Harper Pauline Jackson Mark D Lyttle Colin VE Powell Louise Rogers Damian Roland Wolfgang Stöhr Kate Sturgeon Elia Vitale Mandy Wan Diana M Gibb Mike Sharland
author_facet	Sam Barratt Julia A Bielicki David Dunn Saul N Faust Adam Finn Lynda Harper Pauline Jackson Mark D Lyttle Colin VE Powell Louise Rogers Damian Roland Wolfgang Stöhr Kate Sturgeon Elia Vitale Mandy Wan Diana M Gibb Mike Sharland
author_sort	Sam Barratt
title	Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
title_short	Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
title_full	Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
title_fullStr	Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
title_full_unstemmed	Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT
title_sort	amoxicillin duration and dose for community-acquired pneumonia in children: the cap-it factorial non-inferiority rct
publisher	NIHR Journals Library
publishDate	2021
url	https://doaj.org/article/0e90f12c77e941da9612c5c56c0edb52
work_keys_str_mv	AT sambarratt amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT juliaabielicki amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT daviddunn amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT saulnfaust amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT adamfinn amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT lyndaharper amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT paulinejackson amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT markdlyttle amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT colinvepowell amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT louiserogers amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT damianroland amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT wolfgangstohr amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT katesturgeon amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT eliavitale amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT mandywan amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT dianamgibb amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct AT mikesharland amoxicillindurationanddoseforcommunityacquiredpneumoniainchildrenthecapitfactorialnoninferiorityrct
_version_	1718444270186135552
spelling	oai:doaj.org-article:0e90f12c77e941da9612c5c56c0edb522021-11-05T11:35:00ZAmoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT1366-52782046-492410.3310/hta25600https://doaj.org/article/0e90f12c77e941da9612c5c56c0edb522021-11-01T00:00:00Zhttps://doi.org/10.3310/hta25600https://doaj.org/toc/1366-5278https://doaj.org/toc/2046-4924Background: Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children. Objectives: To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a lower and a higher dose at hospital discharge in children with uncomplicated community-acquired pneumonia. Design: A multicentre randomised double-blind 2 × 2 factorial non-inferiority trial in secondary care in the UK and Ireland. Setting: Paediatric emergency departments, paediatric assessment/observation units and inpatient wards. Participants: Children aged > 6 months, weighing 6–24 kg, with a clinical diagnosis of community-acquired pneumonia, in whom treatment with amoxicillin as the sole antibiotic was planned on discharge. Interventions: Oral amoxicillin syrup at a dose of 35–50 mg/kg/day compared with a dose of 70–90 mg/kg/day, and 3 compared with 7 days’ duration. Children were randomised simultaneously to each of the two factorial arms in a 1 : 1 ratio. Main outcome measures: The primary outcome was clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Secondary outcomes included severity and duration of parent/guardian-reported community-acquired pneumonia symptoms, drug-related adverse events (including thrush, skin rashes and diarrhoea), antimicrobial resistance and adherence to trial medication. Results: A total of 824 children were recruited from 29 hospitals. Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6–2.7) years; 52% male] were randomised to either 3 (n = 413) or 7 days (n = 401) of trial medication at either lower (n = 410) or higher (n = 404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval –3.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval –3.7% to 4.0%), both demonstrating non-inferiority. Resolution of cough was faster in the 7-day arm than in the 3-day arm for cough (10 days vs. 12 days) (p = 0.040), with no difference in time to resolution of other symptoms. The type and frequency of adverse events and rate of colonisation by penicillin-non-susceptible pneumococci were comparable between arms. Limitations: End-of-treatment swabs were not taken, and 28-day swabs were collected in only 53% of children. We focused on phenotypic penicillin resistance testing in pneumococci in the nasopharynx, which does not describe the global impact on the microflora. Although 21% of children did not attend the final 28-day visit, we obtained data from general practitioners for the primary end point on all but 3% of children. Conclusions: Antibiotic retreatment, adverse events and nasopharyngeal colonisation by penicillin-non-susceptible pneumococci were similar with the higher and lower amoxicillin doses and the 3- and 7-day treatments. Time to resolution of cough and sleep disturbance was slightly longer in children taking 3 days’ amoxicillin, but time to resolution of all other symptoms was similar in both arms. Future work: Antimicrobial resistance genotypic studies are ongoing, including whole-genome sequencing and shotgun metagenomics, to fully characterise the effect of amoxicillin dose and duration on antimicrobial resistance. The analysis of a randomised substudy comparing parental electronic and paper diary entry is also ongoing. Trial registration: Current Controlled Trials ISRCTN76888927, EudraCT 2016-000809-36 and CTA 00316/0246/001-0006. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 60. See the NIHR Journals Library website for further project information.Sam BarrattJulia A BielickiDavid DunnSaul N FaustAdam FinnLynda HarperPauline JacksonMark D LyttleColin VE PowellLouise RogersDamian RolandWolfgang StöhrKate SturgeonElia VitaleMandy WanDiana M GibbMike SharlandNIHR Journals Libraryarticlecommunity-acquired pneumoniachildrenamoxicillinantibiotic treatment/durationantibiotic treatment/doserandomised controlled trialMedical technologyR855-855.5ENHealth Technology Assessment, Vol 25, Iss 60 (2021)

Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT

Ejemplares similares