title: Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2-59 months: a multicenter, double-blind, randomized, placebo-controlled trial in pakistan.
abstract: BACKGROUND
  world Health Organization (WHO) acute respiratory illness case management guidelines classify children with fast breathing as having pneumonia and recommend treatment with an antibiotic. There is concern that many of these children may not have pneumonia and are receiving antibiotics unnecessarily. This could increase antibiotic resistance in the community. The aim was to compare the clinical outcome at 72 h in children with WHO-defined nonsevere pneumonia when treated with amoxicillin, compared with placebo.
  
  
  METHODS
  we performed a double-blind, randomized, equivalence trial in 4 tertiary hospitals in Pakistan. Nine hundred children aged 2-59 months with WHO defined nonsevere pneumonia were randomized to receive either 3 days of oral amoxicillin (45mg/kg/day) or placebo; 873 children completed the study. All children were followed up on days 3, 5, and 14. The primary outcome was therapy failure defined a priori at 72 h.
  
  
  RESULTS
  in per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50-1.43; P = .60). The multivariate analysis identified history of difficult breathing (OR, 2.86; 95% CI, 1.29-7.23; P = .027) and temperature >37.5°C 100°F at presentation (OR, 1.99; 95% CI, 1.37-2.90; P = .0001) as risk factors for treatment failure by day 5.
  
  
  CONCLUSIONS
  clinical outcome in children aged 2-59 months with WHO-defined nonsevere pneumonia is not different when treated with an antibiotic or placebo. Similar trials are needed in countries with a high burden of pneumonia to rationalize the use of antibiotics in these communities.
authors.affiliation: ARI Research Cell, Children's Hospital, Pakistan Institute of Medical Sciences, Pakistan. tabishhazir@hotmail.com
authors.forename: Tabish
authors.initials: T
authors.lastname: Hazir
authors.forename: Yasir Bin
authors.initials: YB
authors.lastname: Nisar
authors.forename: Saleem
authors.initials: S
authors.lastname: Abbasi
authors.forename: Yusra Pervaiz
authors.initials: YP
authors.lastname: Ashraf
authors.forename: Joza
authors.initials: J
authors.lastname: Khurshid
authors.forename: Perveen
authors.initials: P
authors.lastname: Tariq
authors.forename: Rai
authors.initials: R
authors.lastname: Asghar
authors.forename: Asifa
authors.initials: A
authors.lastname: Murtaza
authors.forename: Tahir
authors.initials: T
authors.lastname: Masood
authors.forename: Sajid
authors.initials: S
authors.lastname: Maqbool
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010154:Pakistan; D010919:Placebos / Q000008:administration & dosage; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D010919:Placebos; D000658:Amoxicillin