title: Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children.
abstract: BACKGROUND
  High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited.
  
  
  OBJECTIVE
  To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM.
  
  
  METHODS
  In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2. Susceptibility to penicillin and amoxicillin was measured by E-test.
  
  
  RESULTS
  Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S. pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1 beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days 4 to 6.
  
  
  CONCLUSIONS
  The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.
authors.affiliation: Pediatric Infectious Disease Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Lolita
authors.initials: L
authors.lastname: Piglansky
authors.forename: Eugene
authors.initials: E
authors.lastname: Leibovitz
authors.forename: Simon
authors.initials: S
authors.lastname: Raiz
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Press
authors.forename: Alberto
authors.initials: A
authors.lastname: Leiberman
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
mesh_terms: D000208:Acute Disease; D000658:Amoxicillin / Q000008:administration & dosage* / Q000494:pharmacology; D016009:Chi-Square Distribution; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D005260:Female; D005500:Follow-Up Studies; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology; D010406:Penicillins / Q000494:pharmacology; D011336:Probability; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D010406:Penicillins; D000658:Amoxicillin