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.
Highlights
Antibiotic resistance occurs when bacteria causing an infection survive after being exposed to a drug that, under normal conditions, would kill it or inhibit its growth [1]
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
The issue of antibiotic resistant bacteria is such that, according to the World Health Organization (WHO) predictions, if antibiotic resistance continues to increase at this rate, infections caused by resistant bacteria will become the top cause of death worldwide, ahead of cancer, diabetes and cardiovascular diseases [3]
Summary
Antibiotic resistance occurs when bacteria causing an infection survive after being exposed to a drug that, under normal conditions, would kill it or inhibit its growth [1] As a result, these surviving strains multiply and spread due to the lack of competition from other strains sensitive to the same drug. Within the critical priority group are carbapenem and 3rd generation cephalosporin resistant Enterobacteriaceae. These bacteria are common pathogens causing severe infections such as bloodstream infections, pneumonia, complicated urinary tract infections and complicated intra-abdominal infections. Enterobacteriaceae posed a threat to the public health due to their ability to become resistant to antibiotics by producing extended-spectrum ß-lactamases (ESBLs) [7]. As guidance to elaborate plans to manage the CRE crisis and develop new new active problem drugs more active drugs more efficiently
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