In vitro activity of the {beta}-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases

J Antimicrob Chemother. 2009 Aug;64(2):326-9. doi: 10.1093/jac/dkp197. Epub 2009 Jun 2.


Background: NXL104 is a novel-structure beta-lactamase inhibitor with potent activity against both class A and class C enzymes. Among the class A carbapenemases, KPC-type enzymes are now spreading rapidly and KPC-related carbapenemase resistance is an emerging phenomenon of great clinical importance. The activity of NXL104 against KPC beta-lactamases was examined.

Methods: Enzymatic activity of purified recombinant KPC-2 was measured with nitrocefin as reporter substrate and inhibition by NXL104 was measured by determination of IC(50) values. Antimicrobial susceptibility testing of various beta-lactams combined with a fixed concentration of NXL104 at 4 mg/L against strains producing KPC enzymes was performed by the broth microdilution method.

Results: NXL104 was a potent inhibitor of KPC-2 with an IC(50) of 38 nM. NXL104 restored the antimicrobial activity of ceftazidime, ceftriaxone, imipenem and piperacillin against Enterobacteriaceae strains producing KPC-2 or KPC-3. MIC values of ceftazidime against KPC producers were reduced by up to 1000-fold by combination with NXL104.

Conclusions: NXL104 inhibitory activity is unique in terms of spectrum, encompassing class A extended-spectrum beta-lactamases, class C enzymes and class A carbapenemases. Given the limited therapeutic options available for infections caused by multiresistant Enterobacteriaceae isolates, NXL104 beta-lactamase inhibitor is a promising agent to be used in combination with a beta-lactam to protect its antibacterial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Cephalosporins / metabolism
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / enzymology*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Molecular Structure
  • beta-Lactamase Inhibitors*
  • beta-Lactamases
  • beta-Lactams / pharmacology*


  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Cephalosporins
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • avibactam
  • beta-lactamase KPC-2
  • beta-Lactamases
  • nitrocefin