Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases

Author:

Ito-Horiyama Tsukasa1,Ishii Yoshikazu2,Ito Akinobu1,Sato Takafumi1,Nakamura Rio1,Fukuhara Norio3,Tsuji Masakatsu1,Yamano Yoshinori1,Yamaguchi Keizo2,Tateda Kazuhiro2

Affiliation:

1. Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan

2. Toho University School of Medicine, Tokyo, Japan

3. Global Innovation Office, Shionogi & Co., Ltd., Osaka, Japan

Abstract

ABSTRACT To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies ( k cat / K m ) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM −1 s −1 , respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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