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

Summary 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...

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Bibliographic Details
Published in:The Lancet infectious diseases 2011-05, Vol.11 (5), p.381-393
Main Authors: Cornaglia, Giuseppe, MD, Giamarellou, Helen, MD, Rossolini, Gian Maria, MD
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
beta-Lactam Resistance - genetics
beta-Lactamases - classification
beta-Lactams - pharmacology
Biological and medical sciences
Gene Expression Regulation, Bacterial - physiology
Gram-Negative Bacteria - drug effects
Gram-Negative Bacteria - enzymology
Gram-Negative Bacteria - genetics
Infectious Disease
Medical sciences
Pharmacology. Drug treatments
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Summary:Summary 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.
ISSN:1473-3099
1474-4457
DOI:10.1016/S1473-3099(11)70056-1