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.

Higher CTX-M, Tem, and SHV Extended-Spectrum Beta-Lactamase Plasmid Gene Combination Frequency in Esbl Producing Klebsiella Pneumoniae Compared With Esbl Producing Escherichia Coli

“…Considerably higher plasmid gene frequency was found in this study compared to the literature for CTX-M+ TEM-SHV+ plasmid gene combination (63.5% vs 4.7-5.98% in literature), as well as CTX-M-TEM+ SHV+ gene combination (47.06% vs 3.42% in literature; Hayakawa et al, 2013;Manoharan et al, 2011). This study's finding of higher bacterial plasmid gene frequency could be explained by the use of different material, i.e., the higher plasmid gene frequency in wound infections compared to urinary tract infections and bacteria strains; higher plasmid gene frequency in ESBL producing K. pneumoniae compared to ESBL producing E. coli; as well as geographical differences in plasmid gene expression among different populations worldwide (Alekshun & Levy, 2007;Shaikh et al, 2015;Lee et al, 2012;Cantón et al, 2008). There is a considerable geographical difference in ESBL producing microorganisms and plasmid gene frequency in European countries.…”

“…genes: CTX-M, TEM, and SHV (Poirel, Naas, & Nordmann, 2008) in the bacterial plasmid genome, each determining a specific resistance towards different antimicrobials (Shaikh et al, 2015;Lee et al, 2012; The New β-Lactamases -NEJM, 2015).…”

“…Plasmid CTX-M, TEM, and SHV genes, and their combinations, which determine antimicrobial resistance and clinical course severity, vary widely depending on the geographic location, hospital, ward, patient group, or even type of infection (Alekshun & Levy, 2007;Shaikh et al, 2015;Lee et al, 2012;Cantón et al, 2008). Therefore, it is essential to determine the local ESBL producing bacteria strains and plasmid extended-spectrum beta-lactamase gene frequency in order to establish local resistance patterns and start an effective empiric antibacterial treatment (Tacconelli et al, 2014).…”

New Treatment Options against Gram-negative Organisms

“…NXL104/ceftazidime combi nation is currently undergoing Phase II clinical trials in patients admitted for complicated intra-abdominal and complicated urinary tract infections [32].…”

“…Ceftobiprole is stable against some enzymes (non-ESBL class A), but is hydrolyzed by ESBLs and carbapenemases [33]. A study published in 2008 reported that ceftobiprole monotherapy was as eff ective as vancomycin combined with ceftazidime for treating patients with a broad range of complicated skin and skinstructure infections and infections due to Gram-positive and Gram-negative bacteria [32]. Ceftobiprole is an eff ective anti-MRSA agent that also has activity against important Gram-negative bacteria, but there is no evidence that ceftobiprole has better activity against class A and class C β-lactamase-producing Gram-negative bacteria compared to ceftazidime.…”