Proliferation and significance of clinically relevant β‐lactamases

Abstract

Inactivation of β‐lactam antibiotics by β‐lactamases in bacterial infections is associated with some of the most serious infectious disease issues that are currently encountered. The evolution of unique β‐lactamases has resulted in more than 1,300 distinct enzymes that have been identified in natural clinical isolates. Of these enzymes, the most deleterious β‐lactamases are the extended‐spectrum β‐lactamases, or ESBLs, that hydrolyze most penicillins and cephalosporins, and the carbapenemases that may inactivate all β‐lactam classes of drugs. The most prominent ESBLs worldwide are the CTX‐M‐14 and CTX‐M‐15 enzymes. Among enzyme families, the TEM and OXA β‐lactamases exhibit the greatest number of variants. The broad groups of carbapenemases are particularly treacherous, especially the KPC serine carbapenemases and the NDM family of metallo‐β‐lactamases, both of which appear in multidrug‐resistant Gram‐negative pathogens that are often resistant to most classes of antibiotics. Although new β‐lactamase inhibitor combinations are being investigated as a means of controlling infections caused by these organisms, additional approaches are sorely needed.