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

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 mu M-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 mu M.