New definitions of extended-spectrum β-lactamase conferring worldwide emerging antibiotic resistance

Abstract

Although there is no consensus of the precise definition of ESBL, three kinds of ESBL definitions have been proposed. First, the classical definition includes variants derived from TEM-1, TEM-2, or SHV-1; K1 (KOXY) of Klebsiella oxytoca. Second, the broadened definition has stretched the classical definition of ESBL to include: (1) β-lactamases (CTX-M-ESBLs, GES-ESBLs, and VEB-ESBLs), with spectra similar to those of TEM and SHV variants (designated as TEM- and SHV-ESBLs, respectively) but derived from other sources; (2) TEM and SHV variants with borderline ESBL activity; e.g., TEM-12; and (3) various β-lactamases conferring wider resistance than their parent types but not meeting the definition for group 2be; e.g., OXA-types (OXA-ESBLs) and mutant AmpC-types (AmpC-ESBLs), with increased activity against oxyimino-cephalosporins and with resistance to clavulanic acid. Third, the all-inclusive definition includes: (1) ESBL(A) (named for class A ESBLs); (2) ESBL(M) (miscellaneous ESBLs), which has been subdivided into ESBL(M-C) (class C; plasmid-mediated AmpC) and ESBL(M-D) (class D); and (3) ESBL(CARBA) (ESBLs with hydrolytic activity against carbapenems), which has been subdivided into ESBL(CARBA-A) (class A carbapenemases), ESBL(CARBA-B) (class B carbapenemases), and ESBL(CARBA-D) (class D carbapenemases). The consensus view about the ESBL definition is that the classical ESBL definition must be expanded to class A non-TEM- and non-SHV-ESBLs (CTX-M-, GES-, VEB-ESBLs, etc.). However, these three definitions evoke rational debate on the question "Which would be included in the category of ESBLs among AmpC-ESBLs, OXA-ESBLs, and/or carbapenemases?" Therefore, there is a great need for consensus in the precise definition of ESBL.