Global dissemination of β2-lactamases mediating resistance to cephalosporins and carbapenems

Abstract

While the main era of β-lactam discovery programs is over, these agents continue to be the most widely prescribed antimicrobials in both community and hospital settings. This has led to considerable β-lactam pressure on pathogens, resulting in a literal explosion of new β-lactamase variants of existing enzyme classes. Recent advances in the molecular tools used to detect and characterize β-lactamases and their genes has, in part, fueled the large increase in communications identifying novel β-lactamases, particularly in Gram-negative bacilli. It now seems clear that the β-lactams themselves have shaped the field of new enzymes, and the evolution of key amino acid substitutions around the active sites of β-lactamases continues to drive resistance. Over 130 variants of TEM β-lactamase now exist, and more are reported in the scientific literature each month. The most disturbing current trend is that many bla structural genes normally limited to the chromosome are now mobilized on plasmids and integrons, broadening the spread of resistance to include carbapenems and cephamycins. Furthermore, in some Enterobacteriaceae, concomitant loss of outer membrane porins act in concert with these transmissible β-lactamase genes to confer resistance to the most potent β-lactams and inhibitor combinations available. Continued reviews of the literature are necessary in order to keep abreast of the ingenuity with which bacteria are changing the current genetic landscape to confer resistance to this important class of antimicrobials.

• ambler class A, B, C and D β2-lactamases
• β2-lactamases
• carbapenemase
• Escherichia coli
• extended spectrum β2-lactamases
• Klebsiella pneumoniae
• OXA
• SHV
• TEM
• third-generation cephalosporins