Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media

Tebipenem pivoxil, an oral carbapenem antibiotic for pediatric use, exhibits excellent clinical effects on acute otitis media (AOM). The present study was conducted to assess the pharmacokinetic profile of tebipenem in middle ear effusion and to examine the clinical efficacy of tebipenem pivoxil by calculating the values of the pharmacokinetic-pharmacodynamic parameters (AUC/MIC, Cmax/MIC, and T > MIC) of tebipenem at the site of action. Twenty-three pediatric outpatients diagnosed with AOM were enrolled. Ear discharge or nasopharyngeal swabs collected before the onset of oral administration were used to conduct bacteriological examinations, and subjects were then treated by twice-a-day oral administration of tebipenem pivoxil 6 mg/kg. The clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae were obtained from 10 and 19 pediatric patients (8 overlapped), respectively. On day 2 of administration, blood and middle ear effusion were collected from 20 pediatric patients to measure plasma and middle ear concentrations of tebipenem. Consequently, the Cmax and the AUC0-∞ in plasma were 5.3 ± 1.6 μg/ml (mean ± SD) and 7.9 ± 0.2 μg h/ml, respectively. The Cmax in middle ear effusion of tebipenem was 1.2 ± 0.1 μg/ml, exceeding its MIC for these pathogens. The ratio of AUC0-∞ in middle ear effusion to AUC0-∞ in plasma was 0.36, showing the good transfer of tebipenem into the effusion; this result corroborated the known high rate of clinical efficacy of tebipenem pivoxil for patients with AOM and the low incidence of recurrence in them as manifested by the healing rate of 94.1 % (16/17).