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Clin Infect Dis. 2015 Apr 15;60(8):1216-24. doi: 10.1093/cid/ciu1166. Epub 2014 Dec 30.

Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial.

Author information

1
Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.
2
Medical Research Council Tropical Epidemiology Group, Department of Infectious Disease Epidemiology.
3
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, United Kingdom.
4
Department of Paediatrics and Child Health, University of Nairobi, Kenya.
5
Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi Nuffield Department of Medicine, University of Oxford, United Kingdom.

Abstract

BACKGROUND:

There are concerns that the evidence from studies showing noninferiority of oral amoxicillin to benzyl penicillin for severe pneumonia may not be generalizable to high-mortality settings.

METHODS:

An open-label, multicenter, randomized controlled noninferiority trial was conducted at 6 Kenyan hospitals. Eligible children aged 2-59 months were randomized to receive amoxicillin or benzyl penicillin and followed up for the primary outcome of treatment failure at 48 hours. A noninferiority margin of risk difference between amoxicillin and benzyl penicillin groups was prespecified at 7%.

RESULTS:

We recruited 527 children, including 302 (57.3%) with comorbidity. Treatment failure was observed in 20 of 260 (7.7%) and 21 of 261 (8.0%) of patients in the amoxicillin and benzyl penicillin arms, respectively (risk difference, -0.3% [95% confidence interval, -5.0% to 4.3%]) in per-protocol analyses. These findings were supported by the results of intention-to-treat analyses. Treatment failure by day 5 postenrollment was 11.4% and 11.0% and rising to 13.5% and 16.8% by day 14 in the amoxicillin vs benzyl penicillin groups, respectively. The most frequent cause of cumulative treatment failure at day 14 was clinical deterioration within 48 hours of enrollment (33/59 [55.9%]). Four patients died (overall mortality 0.8%) during the study, 3 of whom were allocated to the benzyl penicillin group. The presence of wheeze was independently associated with less frequent treatment failure.

CONCLUSIONS:

Our findings confirm noninferiority of amoxicillin to benzyl penicillin, provide estimates of risk of treatment failure in Kenya, and offer important additional evidence for policy making in sub-Saharan Africa.

CLINICAL TRIAL REGISTRATION:

NCT01399723.

KEYWORDS:

World Health Organization; amoxicillin; childhood pneumonia; sub-Saharan Africa; treatment failure

PMID:
25550349
PMCID:
PMC4370168
DOI:
10.1093/cid/ciu1166
[Indexed for MEDLINE]
Free PMC Article

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