title: Comparison of oral amoxicillin given thrice or twice daily to children between 2 and 59 months old with non-severe pneumonia: a randomized controlled trial.
abstract: OBJECTIVE
  Oral amoxicillin (50 mg/kg/day) thrice daily is the first-line therapy for non-severe childhood pneumonia. Compliance could be enhanced if two daily doses are employed. We assessed the equivalence of oral amoxicillin (50 mg/kg/day) thrice or twice daily in those patients.
  
  
  METHODS
  This randomized (1 : 1), controlled, triple-blinded investigation conducted at one centre in Brazil included children aged 2-59 months with non-severe pneumonia diagnosed by trained paediatricians based on respiratory complaints and radiographic pulmonary infiltrate/consolidation. Participants were randomly assigned to receive one bottle (Amoxicillin 1) at 6 am, 2 pm and 10 pm and the other bottle (Amoxicillin 2) at 8 am and 8 pm: one bottle contained amoxicillin and the other placebo and vice versa. Only the pharmacist knew patients' allocation. Follow-up assessments were done at 2, 5 and 14 days after enrolment. Chest radiographs were read by three independent radiologists. Primary outcome was treatment failure (development of danger signs, persistence of fever, tachypnoea, development of serious adverse reactions, death and withdrawal from the trial) at 48 h. ClinicalTrials.gov: identifier NCT01200706.
  
  
  RESULTS
  Four hundred and twelve and 408 participants received amoxicillin thrice or twice daily, respectively. Treatment failure was detected in 94 (22.8%) and 94 (23.0%) patients in intention-to-treat analysis (risk difference 0.2%; 95% CI: -5.5%-6.0%) and in 80 (20.1%) and 85 (21.3%) patients in per-protocol analysis (risk difference 1.2%; 95% CI: -4.4%-6.8%). Pneumonia was radiologically confirmed by concordant reading in 277 (33.8%) cases, among whom treatment failure was registered in 25/133 (18.8%) and 27/144 (18.8%) participants from the thrice and twice daily doses subgroups, respectively (risk difference -0.05%; 95% CI: -9.3%-9.2%).
  
  
  CONCLUSIONS
  Oral amoxicillin (50 mg/kg/day) twice daily is as efficacious as thrice daily.
authors.affiliation: Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Ana-Luisa
authors.initials: AL
authors.lastname: Vilas-Boas
authors.affiliation: Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Maria-Socorro H
authors.initials: MS
authors.lastname: Fontoura
authors.affiliation: Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Xavier-Souza
authors.affiliation: Department of Image Diagnosis, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: César A
authors.initials: CA
authors.lastname: Araújo-Neto
authors.affiliation: Image Diagnosis Unit, Federal University of Bahia Hospital, Salvador, Brazil.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Andrade
authors.affiliation: Department of Image Diagnosis, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Rosa V
authors.initials: RV
authors.lastname: Brim
authors.affiliation: Pharmacy Unit, Federal University of Bahia Hospital, Salvador, Brazil.
authors.forename: Lucia
authors.initials: L
authors.lastname: Noblat
authors.affiliation: Pathology Department, Federal University of Bahia School of Medicine and Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: Department of Epidemiology, University of São Paulo School of Public Health, São Paulo, Brazil.
authors.forename: Maria-Regina A
authors.initials: MR
authors.lastname: Cardoso
authors.affiliation: Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil nascimentocarvalho@hotmail.com.
authors.forename: Cristiana M
authors.initials: CM
authors.lastname: Nascimento-Carvalho
mesh_terms: D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001938:Brazil; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin
keywords: acute respiratory infections; antibacterials; antimicrobial therapy; lower respiratory tract infection