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Efficacy and Pharmacokinetics of the Combination of OP0595 and Cefepime in a Mouse Model of Pneumonia Caused by Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae
http://hdl.handle.net/10069/37699
http://hdl.handle.net/10069/37699134c0c1a-dee4-4348-8772-7413c2627a4f
名前 / ファイル | ライセンス | アクション |
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AAC61_828-17.pdf (423.5 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-02-01 | |||||
タイトル | ||||||
タイトル | Efficacy and Pharmacokinetics of the Combination of OP0595 and Cefepime in a Mouse Model of Pneumonia Caused by Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ESBLs | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Klebsiella pneumoniae | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | serine-beta-lactamase inhibitor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | diazabicyclooctane | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kaku, Norihito
× Kaku, Norihito× Kosai, Kosuke× Takeda, Kazuaki× Uno, Naoki× Morinaga, Yoshitomo× Hasegawa, Hiroo× Miyazaki, Taiga× Izumikawa, Koichi× Mukae, Hiroshi× Yanagihara, Katsunori |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | OP0595 (RG6080) is a novel diazabicyclooctane that inhibits class A and C serine beta-lactamases. Although the combination of OP0595 and cefepime (FEP) showed good in vitro activity against extended-spectrum-beta-lactamase (ESBL)-producing pathogens, the effect of the combination therapy against severe infections, such as pneumonia or bacteremia, remains unknown in vivo. In this study, we investigated the efficacy and pharmacokinetics of the combination therapy of OP0595 and FEP in a mouse model of pneumonia caused by Klebsiella pneumoniae harboring SHV- and CTX-M-9-type ESBLs. The infected BALB/c mice were intraperitoneally administered saline (control), 100 mg/kg of body weight of FEP, 20 mg/kg of OP0595, or both FEP and OP0595, twice a day. The MIC of FEP against the bacteria was 8 mg/liter and markedly improved to 0.06 mg/liter with the addition of 0.5 mg/ml of OP0595. In the survival study, the combination of FEP and OP0595 significantly improved the survival rate compared with that reported with either OP0595 or FEP alone (P < 0.001). The number of bacteria in the lungs and blood significantly decreased in the combination therapy group compared to that reported for the monotherapy groups (P < 0.001). In addition, the in vivo effect depended on the dose of FEP. However, pharmacokinetic analysis revealed that the percentage of time above MIC remained constant when increasing the dose of FEP in combination with 20 mg/kg of OP0595. The results of our study demonstrated the in vivo effectiveness of the combination of OP0595 and FEP. | |||||
書誌情報 |
Antimicrobial Agents and Chemotherapy 巻 61, 号 7, p. e00828-17, 発行日 2017-07 |
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出版者 | ||||||
出版者 | American Society for Microbiology | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00664804 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 10986596 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1128/AAC.00828-17 | |||||
権利 | ||||||
権利情報 | c 2017 American Society for Microbiology | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Antimicrobial Agents and Chemotherapy, 61(7), e00828-17; 2017 |