Comparison of 3 Days Amoxicillin Versus 5 Days Co-Trimoxazole for Treatment of Fast-breathing Pneumonia by Community Health Workers in Children Aged 2-59 Months in Pakistan: A Cluster-randomized Trial.
Administration, Oral
Amoxicillin
/ administration & dosage
Anti-Bacterial Agents
/ administration & dosage
Child, Preschool
Drug Administration Schedule
Female
Humans
Infant
Infant, Newborn
Male
Pakistan
Pneumonia, Bacterial
/ drug therapy
Retrospective Studies
Treatment Failure
Trimethoprim, Sulfamethoxazole Drug Combination
/ administration & dosage
cluster-randomized trial
community treatment
fast-breathing pneumonia
oral amoxicillin
short-course therapy
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
18 07 2019
18 07 2019
Historique:
received:
22
05
2018
accepted:
22
11
2018
pubmed:
1
1
2019
medline:
14
8
2020
entrez:
1
1
2019
Statut:
ppublish
Résumé
Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level. We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2-59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol. Out of the 15 749 cases enrolled in the study, 9153 cases in intervention and 6509 cases in control clusters were included in the analysis. Treatment failure rates were 3.6% (326) in intervention clusters and 9.1% (592) in control clusters. After adjusting for clustering, the risk of treatment failure was lower in intervention clusters (risk difference [RD] -5.5%, 95% confidence interval [CI] -7.4--3.7%) than in control clusters. Children with incomplete adherence had a small increase in treatment failure versus those with complete adherence (RD 2.9%, 95% CI 1.6-4.1%). No deaths or serious adverse events occurred. A 3-day course of oral amoxicillin, administered by LHWs, is an effective and safe treatment for fast-breathing pneumonia in children 2-59 months of age. A shorter course of amoxicillin improves adherence to therapy, is low in cost, and puts less pressure on antimicrobial resistance. ISRCTN10618300.
Sections du résumé
BACKGROUND
Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level.
METHODS
We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2-59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol.
RESULTS
Out of the 15 749 cases enrolled in the study, 9153 cases in intervention and 6509 cases in control clusters were included in the analysis. Treatment failure rates were 3.6% (326) in intervention clusters and 9.1% (592) in control clusters. After adjusting for clustering, the risk of treatment failure was lower in intervention clusters (risk difference [RD] -5.5%, 95% confidence interval [CI] -7.4--3.7%) than in control clusters. Children with incomplete adherence had a small increase in treatment failure versus those with complete adherence (RD 2.9%, 95% CI 1.6-4.1%). No deaths or serious adverse events occurred.
CONCLUSIONS
A 3-day course of oral amoxicillin, administered by LHWs, is an effective and safe treatment for fast-breathing pneumonia in children 2-59 months of age. A shorter course of amoxicillin improves adherence to therapy, is low in cost, and puts less pressure on antimicrobial resistance.
CLINICAL TRIALS REGISTRATION
ISRCTN10618300.
Identifiants
pubmed: 30596964
pii: 5265227
doi: 10.1093/cid/ciy918
pmc: PMC6637273
doi:
Substances chimiques
Anti-Bacterial Agents
0
Amoxicillin
804826J2HU
Trimethoprim, Sulfamethoxazole Drug Combination
8064-90-2
Banques de données
ISRCTN
['ISRCTN10618300']
Types de publication
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-404Subventions
Organisme : World Health Organization
ID : 001
Pays : International
Organisme : NIAID NIH HHS
ID : K01 AI083097
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Bull World Health Organ. 2004 Jul;82(7):509-15
pubmed: 15508195
Lancet. 2013 Apr 20;381(9875):1405-1416
pubmed: 23582727
Clin Infect Dis. 2017 Jan 15;64(2):184-189
pubmed: 27941119
Int J Epidemiol. 2010 Apr;39 Suppl 1:i155-71
pubmed: 20348118
BMJ. 2006 Sep 23;333(7569):629
pubmed: 16923771
Emerg Infect Dis. 2005 Jun;11(6):802-7
pubmed: 15963272
Lancet. 2015 Jan 31;385(9966):430-40
pubmed: 25280870
Clin Infect Dis. 2011 Feb 1;52(3):293-300
pubmed: 21189270
Lancet Infect Dis. 2015 Apr;15(4):439-50
pubmed: 25769269
Am J Trop Med Hyg. 2012 Nov;87(5 Suppl):6-10
pubmed: 23136272
PLoS One. 2008 Apr 23;3(4):e1991
pubmed: 18431478
Bull World Health Organ. 1996;74(5):501-7
pubmed: 9002330
Lancet. 1991 Jan 19;337(8734):156-9
pubmed: 1670799
Lancet. 2002 Sep 14;360(9336):835-41
pubmed: 12243918
Lancet. 2011 Nov 19;378(9805):1796-803
pubmed: 22078721
Lancet. 1998 Jul 25;352(9124):270-4
pubmed: 9690406
Pediatr Infect Dis J. 2014 Feb;33(2):136-42
pubmed: 23989106
Lancet Infect Dis. 2003 Sep;3(9):547-56
pubmed: 12954560
JAMA. 2001 Jul 4;286(1):49-56
pubmed: 11434826
J Trop Pediatr. 2008 Dec;54(6):382-9
pubmed: 18611959
BMJ. 2004 Apr 3;328(7443):791
pubmed: 15070633