Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media
- Rinya Sugita
- … show all 1 hide
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
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, C max/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 C max and the AUC0–∞ in plasma were 5.3 ± 1.6 μg/ml (mean ± SD) and 7.9 ± 0.2 μg h/ml, respectively. The C max 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).
- Kobayashi R, Konomi M, Hasegawa K, Morozumi M, Sunakawa K, Ubukata K. In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillin-nonsusceptible Streptococcus pneumoniae. Antimicrob Agents Chemother. 2005;49:889–94. CrossRef
- Kishii K, Chiba N, Morozumi M, Ono A, Ida T, Ubukata K. In vitro activity of tebipenem, a new oral carbapenem antibiotic, against beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 2010;54:3970–3. CrossRef
- Sunakawa K. Pharmacological properties and clinical performance of the novel oral carbapenem antimicrobial drug “tebipenem pivoxil”. Jpn J Chemother. 2009;57:279–94.
- Sato N, Kijima K, Koresawa T, Mitomi N, Morita J, Suzuki H, et al. Population pharmacokinetics of tebipenem pivoxil (ME1211), a novel oral carbapenem antibiotic, in pediatric patients with otolaryngological infection or pneumonia. Drug Metab Pharmacokinet. 2008;23:434–46. CrossRef
- Sugano T, Yoshida T, Yamada K, Shimizu A, Morita J, Kijima K, et al. Antimicrobial activity of tebipenem pivoxil against Streptococcus pneumoniae and Haemophilus influenzae, and its pharmacokinetic-pharmacodynamic profile in mice. Jpn J Chemother. 2009;57(suppl 1):38–48.
- Totsuka K, Aizawa K, Morita J, Hori S, Iwata S, Sunakawa K. PK–PD analysis of tebipenem pivoxil in clinical trials for pediatric patients. Jpn J Chemother. 2009;57(suppl 1):186–91.
- American Academy of Pediatrics, Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451–65. CrossRef
- Subcommittee on Clinical Practice Guidelines for the Diagnosis and Management of Acute Otitis Media in Children (eds) 2009. The 2009 clinical practice guidelines for the diagnosis and treatment of acute otitis media (AOM) in children. Japan Otological Society, Japan Society for Pediatric Otorhinolaryngology, Japan Society for Infectious Diseases in Otorhinolaryngology. Kanehara Shuppan, Tokyo
- Suzuki K, Baba S, Totsuka K, Hori S, Ubukata K, Nakashima M, et al. Double-blind comparative study of tebipenem pivoxil and high-dose cefditoren pivoxil in children with acute otitis media (phase III). Jpn J Chemother. 2009;57(suppl 1):167–85.
- Craig WA. The role of pharmacodynamics in effective treatment of community-acquired pathogens. Adv Stud Med. 2002;2:126–34.
- Harrison CJ. Using antibiotic concentrations in middle ear fluid to predict potential clinical efficacy. Pediatr Infect Dis J. 1997;16:S12–6. CrossRef
- Nicolau DP, Sutherland CA, Arguedas A, Dagan R, Pichichero ME. Pharmacokinetics of cefprozil in plasma and middle ear fluid: in children undergoing treatment for acute otitis media. Paediatr Drugs. 2007;9:119–23. CrossRef
- Hotomi M, Yamanaka N, Billal DS, Sakai A, Yamauchi K, Suzumoto M, et al. Genotyping of Streptococcus pneumoniae and Haemophilus influenzae isolated from paired middle ear fluid and nasopharynx by pulsed-field gel electrophoresis. ORL J Otorhinolaryngol Relat Spec. 2004;66:233–40. CrossRef
- Ouchi K, Kurosaki T, Okada K (eds) (2011) Guidelines for the management of respiratory infectious diseases in children in Japan 2011. Kyowa Kikaku, Tokyo (in Japanese)
- Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media
Journal of Infection and Chemotherapy
Volume 19, Issue 3 , pp 465-471
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Tebipenem pivoxil
- Acute otitis media
- Middle ear effusion
- Industry Sectors
- Rinya Sugita (1)
- Author Affiliations
- 1. Sugita Otorhinolaryngologic Clinic, 3-14-1-401, Takasu, Mihama-ku, Chiba, 261-0004, Japan