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

Metallo-beta-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 beta-lactams. Since the 1990s, several metallo-beta-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-beta-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-beta-lactamase. The spread of metallo-beta-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.