Metallo-β-lactamases: a last frontier for β-lactams?

Lancet Infect Dis. 2011 May;11(5):381-93. doi: 10.1016/S1473-3099(11)70056-1.

Abstract

Metallo-β-lactamases are resistance determinants of increasing clinical relevance in Gram-negative bacteria. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all β-lactams. Since the 1990s, several metallo-β-lactamases encoded by mobile DNA have emerged in important Gram-negative pathogens (ie, in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii). Some of these enzymes (eg, VIM-1 and NDM-1) have been involved in the recent crisis resulting from the international dissemination of carbapenem-resistant Klebsiella pneumoniae and other enterobacteria. Although substantial knowledge about the molecular biology and genetics of metallo-β-lactamases is available, epidemiological data are inconsistent and clinical experience is still lacking; therefore, several unsolved or debatable issues remain about the management of infections caused by producers of metallo-β-lactamase. The spread of metallo-β-lactamases presents a major challenge both for treatment of individual patients and for policies of infection control, exposing the substantial unpreparedness of public health structures in facing up to this emergency.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Gene Expression Regulation, Bacterial / physiology
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacteria / genetics
  • beta-Lactam Resistance / genetics*
  • beta-Lactamases / classification*
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • beta-Lactamases