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In vivo efficacy and pharmacokinetics of tomopenem (CS-023), a novel carbapenem, against Pseudomonas aeruginosa in a murine chronic respiratory tract infection model.


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Title: In vivo efficacy and pharmacokinetics of tomopenem (CS-023), a novel carbapenem, against Pseudomonas aeruginosa in a murine chronic respiratory tract infection model.
Authors: Morinaga, Yoshitomo / Yanagihara, Katsunori / Nakamura, Shigeki / Yamamoto, Kazuko / Izumikawa, Koichi / Seki, Masafumi / Kakeya, Hiroshi / Yamamoto, Yoshihiro / Yamada, Yasuaki / Kohno, Shigeru / Kamihira, Shimeru
Issue Date: Dec-2008
Publisher: Oxford University Press
Citation: The Journal of Antimicrobial Chemotherapy, 62(6), pp.1326-1331; 2008
Abstract: OBJECTIVES: Tomopenem (CS-023) is a novel parenteral carbapenem with broad-spectrum activity against Gram-positive and -negative bacteria, as well as potent activity against drug-resistant pathogens, including penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. We compared the in vivo activity of tomopenem and that of meropenem in a chronic lower respiratory infection mouse model of P. aeruginosa. METHODS: Mice with chronic airway infection by P. aeruginosa were treated with saline (as the control, twice daily), tomopenem (100 mg/kg, twice daily) or meropenem (100 mg/kg, twice daily) for 7 days. After treatment, the number of viable bacteria in lungs and histopathological findings were analysed. The pharmacokinetics of tomopenem and meropenem were also analysed after initial treatment. RESULTS: The number of viable bacteria in lungs treated with saline, tomopenem or meropenem was 4.21 +/- 1.28, 2.91 +/- 0.87 and 3.01 +/- 1.00 log(10) cfu/lung (mean +/- SEM), respectively (P < 0.05, control versus tomopenem- or meropenem-treated groups). In the histopathological examination of lung specimens, the control group had the features of chronic bronchial infection; however, tomopenem- and meropenem-treated groups had fewer inflammatory cells compared with the control group. The pharmacokinetic parameter of % time above MIC for tomopenem and meropenem was 16% and 17% in sera and 15% and 18% in lungs, respectively. CONCLUSIONS: Tomopenem significantly reduced the number of viable bacteria in a murine model of chronic airway infection by P. aeruginosa, compared with the control. Considering the longer half-life of tomopenem in humans compared with most other carbapenems, tomopenem treatment of chronic airway infection with P. aeruginosa is expected to be efficacious.
Keywords: Chronic respiratory infections / Meropenem / P. aeruginosa
URI: http://hdl.handle.net/10069/22670
ISSN: 03057453
DOI: 10.1093/jac/dkn411
PubMed ID: 18835805
Rights: © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org / This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The definitive publisher-authenticated version The Journal of antimicrobial chemotherapy, 62(6), pp.1326-1331; 2008 is available online at: http://jac.oxfordjournals.org/cgi/content/abstract/62/6/1326 .
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22670

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