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Metallo-beta-lactamases: the quiet before the storm?

Timothy R Walsh1, Mark A Toleman, Laurent Poirel

  • 1Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. t.r.walsh@bristol.ac.uk

Clinical Microbiology Reviews
|April 16, 2005
PubMed

Insights

Metallo-beta-lactamases (MBLs) are dramatically increasing, conferring broad-spectrum antibiotic resistance. Urgent surveillance and inhibitor studies are needed to preserve essential anti-infectives.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Metallo-beta-lactamases (MBLs) are enzymes conferring resistance to beta-lactam antibiotics.
  • Their prevalence is increasing, particularly in Gram-negative bacteria like Pseudomonas aeruginosa.
  • MBLs hydrolyze all beta-lactams and currently lack clinical inhibitors.

Purpose of the Study:

  • To highlight the clinical significance and rapid dissemination of MBLs.
  • To emphasize the need for surveillance and inhibitor development.
  • To discuss the genetic mechanisms facilitating MBL spread.

Main Methods:

  • Literature review and synthesis of existing data on MBL prevalence and characteristics.
  • Analysis of genetic elements (integrons, transposons) associated with MBL gene acquisition.
  • Review of reported MBL types (IMP, VIM, SPM, GIM) and geographical distribution.

Main Results:

  • Nearly 30% of imipenem-resistant Pseudomonas aeruginosa strains harbor MBLs.
  • MBLs confer broad-spectrum beta-lactam resistance, though resistance levels vary in Acinetobacter spp. and Enterobacteriaceae.
  • MBL genes are often located on mobile genetic elements, facilitating rapid spread, sometimes alongside aminoglycoside resistance genes.

Conclusions:

  • The rise of MBLs poses a significant threat to current antibiotic therapies.
  • Effective surveillance and the development of MBL inhibitors are crucial for combating antimicrobial resistance.
  • The genetic mobility of MBLs necessitates global monitoring and strategic interventions.

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