title: Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.
abstract: OBJECTIVE
  To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP).
  
  
  METHODS
  In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy.
  
  
  RESULTS
  Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM.
  
  
  CONCLUSIONS
  On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.
authors.affiliation: Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. rdagan@bgumail.bgu.ac.il
authors.forename: R
authors.initials: R
authors.lastname: Dagan
authors.forename: A
authors.initials: A
authors.lastname: Hoberman
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: E L
authors.initials: EL
authors.lastname: Leibovitz
authors.forename: A
authors.initials: A
authors.lastname: Arguedas
authors.forename: F V
authors.initials: FV
authors.lastname: Rose
authors.forename: B R
authors.initials: BR
authors.lastname: Wynne
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobs
mesh_terms: D000208:Acute Disease; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology*; D010403:Penicillin Resistance; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination