Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from gram-negative bacteria

Annu Rev Microbiol. 2011;65:455-78. doi: 10.1146/annurev-micro-090110-102911.


β-Lactamase evolution presents to the infectious disease community a major challenge in the treatment of infections caused by multidrug-resistant gram-negative bacteria. Because over 1,000 of these naturally occurring β-lactamases exist, attempts to correlate structure and function have become daunting. Although new enzymes in the extended-spectrum β-lactamase (ESBL) families are frequently identified, the older CTX-M-14 and CTX-M-15 enzymes have become the most prevalent ESBLs in global surveillance. Carbapenemases with either serine-based or zinc-facilitated hydrolysis mechanisms are posing some of the most critical problems. Most geographical regions now report KPC serine carbapenemases and the metallo-β-lactamases VIM, IMP, and NDM-1, even though NDM-1 was only recently identified. The rapid emergence of these newer enzymes, with multiple β-lactamases appearing in a single organism, makes the design of new β-lactamase inactivators or β-lactamase-stable β-lactams all the more difficult. Combination therapy will likely be required to counteract the continuing evolution of these insidious enzymes in multidrug-resistant pathogens.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Multiple, Bacterial
  • Enzyme Inhibitors / pharmacology
  • Gram-Negative Bacteria / chemistry
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / epidemiology
  • Gram-Negative Bacterial Infections / microbiology*
  • Humans
  • beta-Lactamase Inhibitors
  • beta-Lactamases / chemistry*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • beta-Lactamases