Carbapenemases: Partners in crime

Carbapenemases, beta-lactamases that inactivate carbapenems and most beta-lactam antibiotics, are most widely known for their ability to confer resistance to beta-lactams. They include serine carbapenemases, such as the widespread KPC family of enzymes, and the metallo-beta-lactamases that contain the IMP, NDM and VIM enzyme families acquired by Gram-negative bacteria on transferable elements. These enzymes are almost always produced by organisms that encode at least one other beta-lactamase, with as many as eight different beta-lactamase genes detected in a single isolate. This consortium of beta-lactamases includes a full spectrum of molecular and biochemical characteristics, providing the producing organism with a range of catalytic activities. In addition to the variety of beta-lactamases found in carbapenemase-producing Gram-negative pathogens are multiple other resistance factors, especially aminoglycoside-modifying enzymes and 16S rRNA methylases that confer resistance to aminoglycosides. Other acquired genes encode fluoroquinolone, trimethoprim, sulfonamide, rifampicin and chloramphenicol resistance determinants on mobile elements that travel together with beta-lactamase genes. Thus, the recent proliferation of transferable carbapenemases serves to magnify resistance to virtually all antibiotic classes. Judicial use of current antibiotics and a quest for novel antibacterial agents are necessary, as multidrug-resistant bacteria continue to multiply. (C) 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.