title: A placebo-controlled trial of antimicrobial treatment for acute otitis media.
abstract: BACKGROUND
  The efficacy of antimicrobial treatment in children with acute otitis media remains controversial.
  
  
  METHODS
  In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media.
  
  
  RESULTS
  Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P<0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P<0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P<0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04).
  
  
  CONCLUSIONS
  Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Tähtinen
authors.forename: Miia K
authors.initials: MK
authors.lastname: Laine
authors.forename: Pentti
authors.initials: P
authors.lastname: Huovinen
authors.forename: Jari
authors.initials: J
authors.lastname: Jalava
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: Aino
authors.initials: A
authors.lastname: Ruohola
mesh_terms: D000208:Acute Disease; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004485:Eczema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007223:Infant; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D010033:Otitis Media / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination