Large dosage amoxicillin/clavulanate, compared with azithromycin, for the treatment of bacterial acute otitis media in children.
BACKGROUND
A large dosage pediatric formulation of amoxicillin/clavulanate with an improved pharmacokinetic/pharmacodynamic profile was developed to eradicate many penicillin-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae (including beta-lactamase-producing strains).


METHODS
This randomized, investigator-blinded, multicenter trial examined treatment of bacterial acute otitis media (AOM) in children 6-30 months of age with amoxicillin/clavulanate (90/6.4 mg/kg/d in 2 divided doses for 10 days) versus azithromycin (10 mg/kg for 1 day followed by 5 mg/kg/d for 4 days). Tympanocentesis was performed at entry for bacteriologic assessment, at the on-therapy visit (day 4-6) to determine bacterial eradication and at any time before the end-of-therapy visit (day 12-14) if the child was categorized as experiencing clinical failure. Clinical assessments were performed at the on-therapy, end-of-therapy and follow-up (day 21-25) visits.


RESULTS
We enrolled 730 children; AOM pathogens were isolated at baseline for 249 of the amoxicillin/clavulanate group and 245 of the azithromycin group. For children with AOM pathogens at baseline, clinical success rates at the end-of-therapy visit were 90.5% for amoxicillin/clavulanate versus 80.9% for azithromycin (P < 0.01), and those at the on-therapy and follow-up visits were 94.9% versus 88.0% and 80.3% versus 71.1%, respectively (all P < 0.05). At the on-therapy visit, pretherapy pathogens were eradicated for 94.2% of children receiving amoxicillin/clavulanate versus 70.3% of those receiving azithromycin (P < 0.001). Amoxicillin/clavulanate eradicated 96.0% of S. pneumoniae (92.0% of fully penicillin-resistant S. pneumoniae) and 89.7% of H. influenzae (85.7% [6 of 7 cases] of beta-lactamase-positive H. influenzae). Corresponding rates for azithromycin were 80.4% (54.5%) for S. pneumoniae and 49.1% (100% [1 of 1 case]) for H. influenzae (all P < 0.01 for between-drug comparisons).


CONCLUSIONS
Amoxicillin/clavulanate was clinically and bacteriologically more effective than azithromycin among children with bacterial AOM, including cases caused by penicillin-resistant S. pneumoniae and beta-lactamase-positive H. influenzae.
Hoberman
Alejandro
A
Children's Hospital of Pittsburgh, PA 15213, USA. hoberman@chp.edu
Dagan
Ron
R
Leibovitz
Eugene
E
Rosenblut
Andres
A
Johnson
Candice E
CE
Huff
Anne
A
Bandekar
Rajesh
R
Wynne
Brian
B
D000208:Acute Disease; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; 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
D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; D017963:Azithromycin