Class A carbapenemases

Abstract

Carbapenems, such as imipenem and meropenem, are most often used to treat infections caused by enterobacteria that produce extended-spectrum beta-lactamases, and the emergence of enzymes capable of inactivating carbapenems would therefore limit the options for treatment. Carbapenem resistance in Enterobacteriaceae is rare, but class A beta-lactamases with activity against the carbapenems are becoming more prevalent within this bacterial family. The class A carbapenemases can phylogenetically be segregated into six different groups of which four groups are formed by members of the GES, KPC, SME, IMI/NMC-A enzymes, while SHV-38 and SFC-1 each separately constitute a group. The genes encoding the class A carbapenemases are either plasmid-borne or located on the chromosome of the host. The bla(GES) genes reside as gene cassettes on mainly class I integrons, whereas the bla(KPC) genes and a single bla(IMI-2) gene are flanked by transposable elements on plasmids. Class A carbapenemases hydrolyse penicillins, classical cephalosporins, monobactam, and imipenem and meropenem, and the enzymes are divided into four phenotypically different groups, namely group 2br, 2be, 2e and 2f, according to the Bush-Jacoby-Medeiros classification system. Class A carbapenemases are inhibited by clavulanate and tazobactam like other class A beta-lactamases.