| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2026-02-17 |
| タイトル |
|
|
タイトル |
Efficacy of cefiderocol in murine models of ventilator-associated pneumonia caused by carbapenem-resistant non-fermenting Gram-negative bacilli, with pharmacokinetic evaluation |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
ventilator-associated pneumonia |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Pseudomonas aeruginosa |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Acinetobacter baumannii |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
cefiderocol |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
pharmacokinetics |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
mouse model |
| 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 |
Ota, Kenji
Kaku, Norihito
Mitsumoto-Kaseida, Fujiko
Uno, Naoki
Kosai, Kosuke
Takazono, Takahiro
Hasegawa, Hiroo
Sakamoto, Kei
Morinaga, Yoshitomo
Izumikawa, Koichi
Mukae, Hiroshi
Mikamo, Hiroshige
Yanagihara, Katsunori
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant non-fermenting Gram-negative bacilli poses a serious clinical challenge due to limited treatment options. Cefiderocol (CFDC) is a novel cephalosporin with a catechol moiety that mimics siderophore function, enabling targeted antimicrobial activity against these pathogens. We evaluated the in vivo efficacy of CFDC against carbapenem-resistant Pseudomonas aeruginosa (CR-Pa) and Acinetobacter baumannii (CR-Ab) using murine models of VAP. VAP was induced in neutropenic mice by intratracheal inoculation of bacterial suspension, following endotracheal tube placement to mimic VAP. Pharmacokinetics (PK) analysis was performed to determine CFDC dosing regimens that achieved 70% of the time above the minimum inhibitory concentration (fT > MIC) over 24 h in plasma, which was the average value reported in previous non-clinical studies. In VAP caused by a strain of CR-Ab, CFDC significantly improved the survival rate and reduced bacterial load in the lungs with fT > MIC of 70%. However, in VAP caused by a strain of CR-Pa, CFDC did not significantly improve the survival rate or reduce bacterial load in the lungs, even with fT > MIC of 70%. To evaluate whether a higher fT > MIC of CFDC would enhance in vivo efficacy, we assessed the bactericidal effect at higher fT > MIC values. A significant reduction in bacterial load in the lungs was observed in VAP caused by CR-Pa when fT > MIC exceeded 90%. These findings suggest that the optimal CFDC dosing regimen for VAP may differ depending on the causative pathogen, with higher fT > MIC targets potentially necessary for infections caused by P. aeruginosa. |
|
言語 |
en |
| 書誌情報 |
en : Microbiology Spectrum
巻 14,
号 2,
p. art. no. e0256825,
発行日 2025-12-23
|
| 出版者 |
|
|
出版者 |
American Society for Microbiology |
|
言語 |
en |
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
2165-0497 |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1128/spectrum.02568-25 |
| 権利 |
|
|
権利情報 |
© 2025 Ota et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
|
言語 |
en |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 引用 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Microbiology spectrum, 14(2), art. no. e0256825; 2025 |
|
言語 |
en |
MS14_e0256825.pdf (451 KB)
