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

Clin Infect Dis. 2011 Feb 1;52(3):293-300. doi: 10.1093/cid/ciq142. Epub 2010 Dec 28.

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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / administration & dosage*
  • Anti-Bacterial Agents / administration & dosage*
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Male
  • Pakistan
  • Placebos / administration & dosage
  • Pneumonia / drug therapy*
  • Pneumonia / pathology
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Placebos
  • Amoxicillin