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Carbapenemases

INTRODUCTION

Carbapenem antibiotics have an important antibiotic niche in that they retain activity against the chromosomal cephalosporinases and extended-spectrum beta-lactamases found in many gram-negative pathogens [1,2]. The emergence of carbapenem-hydrolyzing beta-lactamases has threatened the clinical utility of this antibiotic class and brings us a step closer to the challenge of "extreme drug resistance" in gram-negative bacilli [3].

Issues related to carbapenemases will be reviewed here. Penicillinases and cephalosporinases are discussed in detail separately. (See "Extended-spectrum beta-lactamases".)

CLASSIFICATION

Carbapenemases are carbapenem-hydrolyzing beta-lactamases that confer resistance to a broad spectrum of beta-lactam substrates, including carbapenems. This mechanism is distinct from other mechanisms of carbapenem resistance such as impaired permeability due to porin mutations, although the susceptibility patterns for isolates with a carbapenemase and those with porin mutations can be identical.

The carbapenemases have been organized based on amino acid homology in the Ambler molecular classification system. Class A, C, and D beta-lactamases all share a serine residue in the active site, while Class B enzymes require the presence of zinc for activity (and hence are referred to as metallo-beta-lactamases). Classes A, B, and D are of greatest clinical importance among nosocomial pathogens.

Class A beta-lactamases — Class A beta-lactamases are characterized by their hydrolytic mechanisms that require an active-site serine at position 70 [4]. These include penicillinases and cephalosporinases in the TEM, SHV, and CTX-M-type groups (which do not hydrolyze carbapenems), as well as additional groups that possess beta-lactamase (including carbapenemase) activity [1,5]. (See "Extended-spectrum beta-lactamases".)

                      

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Literature review current through: Sep 2014. | This topic last updated: Feb 11, 2014.
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