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Review
. 2019 Aug 19;8(3):122.
doi: 10.3390/antibiotics8030122.

Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections

Beatriz Suay-García  1 , María Teresa Pérez-Gracia  2
Affiliations
Review

Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections

Beatriz Suay-García et al. Antibiotics (Basel). .

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) have become a public health threat worldwide. There are three major mechanisms by which Enterobacteriaceae become resistant to carbapenems: enzyme production, efflux pumps and porin mutations. Of these, enzyme production is the main resistance mechanism. There are three main groups of enzymes responsible for most of the carbapenem resistance: KPC (Klebsiella pneumoniae carbapenemase) (Ambler class A), MBLs (Metallo-ß-Lactamases) (Ambler class B) and OXA-48-like (Ambler class D). KPC-producing Enterobacteriaceae are endemic in the United States, Colombia, Argentina, Greece and Italy. On the other hand, the MBL NDM-1 is the main carbapenemase-producing resistance in India, Pakistan and Sri Lanka, while OXA-48-like enzyme-producers are endemic in Turkey, Malta, the Middle-East and North Africa. All three groups of enzymes are plasmid-mediated, which implies an easier horizontal transfer and, thus, faster spread of carbapenem resistance worldwide. As a result, there is an urgent need to develop new therapeutic guidelines to treat CRE infections. Bearing in mind the different mechanisms by which Enterobacteriaceae can become resistant to carbapenems, there are different approaches to treat infections caused by these bacteria, which include the repurposing of already existing antibiotics, dual therapies with these antibiotics, and the development of new ß-lactamase inhibitors and antibiotics.

Keywords: CRE; Enterobacteriaceae; antibiotic resistance; antimicrobials; carbapenem-resistant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Classification of the different mechanisms of drug resistance in CRE. (Light grey: Ambler class A, White: Ambler class B, Dark grey: Ambler class D) (CRE: Carbapenem-resistant Enterobacteriaceae; CP: carbapenemase producing; KPC: Klebsiella pneumoniae carbapenemase; IMI: Imipenem-hydrolyzing ß-lactamase; GES: Guiana extended-spectrum ß-lactamase; MBLs: Metallo-ß-lactamase; OXA: oxacillinase; NDM: New Delhi metallo-ß-lactamase; VIM: Verona integron-borne metallo-ß-lactamase; IMP: Imipenem-resistant Pseudomonas carbapenemase; SMP: Sao Paulo metallo-ß-lactamase; GIM: German imipenemase; SIM: Seoul imipenemase; AmpC: Type C ampicillinase; ESBLs: Extended-spectrum ß-lactamase).
Figure 2
Figure 2
Timeline representing the introduction of carbapenems and the appearance of carbapenemases worldwide.
See this image and copyright information in PMC

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