Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media.

OBJECTIVES: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). METHODS: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). RESULTS: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). CONCLUSIONS: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.

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). CONCLUSION: 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.