@article{e5ba92c37c72461eb320ba38bcfa6422,
title = "Cefmetazole as an Alternative to Carbapenems Against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Infections Based on In Vitro and In Vivo Pharmacokinetics/Pharmacodynamics Experiments",
abstract = "Purpose: Cefmetazole (CMZ) has received attention as a pharmaceutical intervention for extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) infections. This study aimed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of CMZ against ESBL-EC. Methods: The susceptibility and time-killing activity of CMZ against clinically isolated ESBL-EC (EC9 and EC19) were determined in vitro. The optimal PK/PD index and its target value were calculated based on the results of a PK study in healthy mice and PD study in neutropenic murine thigh infection model mice. Results: The minimum inhibitory concentrations (MICs) of CMZ against EC9 and EC19 were 2.0 and 1.0 µg/mL, respectively. Time–kill studies showed that colony-forming units decreased in a time-dependent manner at CMZ concentrations in the range of 4–64 × MIC. In in vivo PK/PD studies, the antibacterial effect of CMZ showed the better correlation with the time that the free drug concentration remaining above the MIC (fT>MIC), with the target values for a static effect and 1 log10 kill reduction calculated as 57.6% and 69.6%, respectively. Conclusion: CMZ possesses time-dependent bactericidal activities against ESBL-EC and is required to achieve “fT>MIC” ≥ 69.6% for the treatment of ESBL-EC infections.",
keywords = "Beta-lactamase, Cefmetazole, Escherichia coli, Murine thigh infection model, Pharmacokinetics/pharmacodynamics",
author = "Wataru Takemura and Sho Tashiro and Marina Hayashi and Yuki Igarashi and Xiaoxi Liu and Yuki Mizukami and Nana Kojima and Takumi Morita and Yuki Enoki and Kazuaki Taguchi and Yuta Yokoyama and Tomonori Nakamura and Kazuaki Matsumoto",
note = "Funding Information: This work was supported by JSPS KAKENHI (Grant Number JP18K06795). Sho Tashiro wishes to thank the Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan. We would like to thank Editage (www.editage.com ) for English language editing. All authors meet the ICMJE authorship criteria. The authors declare no potential conflicts of interest. Funding Information: This work was supported by JSPS KAKENHI (Grant Number JP18K06795). Sho Tashiro wishes to thank the Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan. We would like to thank Editage ( www.editage.com ) for English language editing. All authors meet the ICMJE authorship criteria. The authors declare no potential conflicts of interest. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
year = "2021",
month = nov,
doi = "10.1007/s11095-021-03140-7",
language = "English",
volume = "38",
pages = "1839--1846",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "11",
}