title: Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial.
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.
  
  
  BACKGROUND
  NCT01399723.
authors.affiliation: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Agweyu
authors.affiliation: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.
authors.forename: David
authors.initials: D
authors.lastname: Gathara
authors.affiliation: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Oliwa
authors.affiliation: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi.
authors.forename: Naomi
authors.initials: N
authors.lastname: Muinga
authors.affiliation: Medical Research Council Tropical Epidemiology Group, Department of Infectious Disease Epidemiology.
authors.forename: Tansy
authors.initials: T
authors.lastname: Edwards
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Allen
authors.affiliation: Department of Paediatrics and Child Health, University of Nairobi, Kenya.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.affiliation: Health Services Unit, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Nairobi Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: English
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007630:Kenya; D008297:Male; D010400:Penicillin G / Q000008:administration & dosage*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D010400:Penicillin G
keywords: World Health Organization; amoxicillin; childhood pneumonia; sub-Saharan Africa; treatment failure