The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria

Abstract

Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.

Keywords: Gram-negative bacteria; KPC; carbapenemases; metallo-β-lactamases; oxacillinases; resistance; β-lactamases.

Figure 1

Worldwide distribution of KPC, NDM, VIM, IMP, SME, SPM, and OXA-48 carbapenemases with a status of dissemination. E = endemic. S = sporadic. N = newly detected. KPC = Klebsiella pneumoniae carbapenemase. NDM = New Delhi metallo-β-lactamase. VIM = Verona-intergon-encoded metallo-β-lactamase. IMP = imipenemase, SME = Serratia marcescens enzyme, SPM = Sao Paulo metallo-β-lactamase. OXA = oxacillinase.