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

Antimicrob Agents Chemother. 2016 Jun 20;60(7):4384-6. doi: 10.1128/AAC.03098-15. Print 2016 Jul.

Abstract

To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies (kcat/Km) 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.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Cephalosporins / chemistry*
  • Cephalosporins / pharmacology
  • Drug Stability
  • Meropenem
  • Siderophores / chemistry*
  • Thienamycins / chemistry
  • Thienamycins / pharmacology
  • beta-Lactamases

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cephalosporins
  • Siderophores
  • Thienamycins
  • beta-Lactamases
  • carbapenemase
  • Meropenem