New Delhi metallo-β-lactamase (NDM-1): an update

J Chemother. 2011 Oct;23(5):263-5. doi: 10.1179/joc.2011.23.5.263.

Abstract

New Delhi metallo-β-lactamase (NDM-1) is a novel broad spectrum carbapenemase with ability to inactivate all β-lactams except aztreonam. However, most of the NDM-1-producers also produce aztreonam hydrolysing-β-lactamases thereby making these pathogens absolutely resistant to all β-lactams. The bla(NDM-1) gene encodes a 27.5 kDa protein of 269 amino acids. It shares very little identity with other metallo-β-lactamases. Maximum identity has been observed to VIM-1/VIM-2 (32.4%). This mini-review is an update of the scientific literature for the said enzyme. Following the recommendation of David livermore, we further propose to combine "aztreonam" and "inhibitor of the most frequently encountered aztreonam hydrolysing-β-lactamases in a given setting" as a possible strategy against NDM-1-producers. The inhibitor should be 'versatile' as well, i.e. it should have the ability to inhibit most of the variants of aztreonam hydrolysing-β-lactamases prevalent in the concerned setting. We strongly recommend surveillance studies using aztreonam/NXL-104-combination against NDM-1-producing pathogens in different geographical regions across the globe.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / pharmacology
  • Azabicyclo Compounds / therapeutic use
  • Aztreonam / administration & dosage
  • Aztreonam / metabolism
  • Aztreonam / pharmacology
  • Aztreonam / therapeutic use
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism*
  • Biotransformation
  • Drug Resistance, Multiple, Bacterial* / drug effects
  • Drug Therapy, Combination
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Global Health
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / enzymology
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / enzymology
  • Gram-Positive Bacterial Infections / drug therapy
  • Humans
  • Molecular Targeted Therapy
  • Sulbactam / administration & dosage
  • Sulbactam / pharmacology
  • Sulbactam / therapeutic use
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism*
  • beta-Lactams / administration & dosage
  • beta-Lactams / metabolism*
  • beta-Lactams / pharmacology
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Bacterial Proteins
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • avibactam
  • beta-Lactamases
  • beta-lactamase NDM-1
  • Aztreonam
  • Sulbactam