Carbapenemases in Enterobacteriaceae: Detection and Antimicrobial Therapy

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) have spread rapidly around the world in the past few years, posing great challenges to human health. The plasmid-mediated horizontal transmission of carbapenem-resistance genes is the main cause of the surge in the prevalence of CRE. Therefore, the timely and accurate detection of CRE, especially carbapenemase-producing Enterobacteriaceae, is very important for the clinical prevention and treatment of these infections. A variety of methods for the rapid detection of CRE phenotypes and genotypes have been developed for use in clinical microbiology laboratories. To overcome the lack of efficient antibiotics, CRE infections are often treated with combination therapies. Moreover, novel drugs and emerging strategies appeared successively and in various stages of development. In this article, we summarized the global distribution of various carbapenemases. And we focused on summarizing and comparing the advantages and limitations of the detection methods and the therapeutic strategies of CRE primarily.

Characterization of Resistance in Gram-Negative Urinary Isolates Using Existing and Novel Indicators of Clinical Relevance: A 10-Year Data Analysis

“…If overall mortality and their economic impact is taken into consideration, the group of "ESKAPE" pathogens, namely E: Enterococcus faecium, S: Staphylococcus aureus or recently Stenotrophomonas maltophilia, K: Klebsiella pneumoniae or recently C: Clostridioides difficile, A: Acinetobacter baumannii, P: Pseudomonas aeruginosa, E: Enterobacter spp., or recently Enterobacteriaceae) present the most clinical challenges [15,16]. A plethora of resistance mechanisms has been described in various bacterial species; some of these resistance mechanisms are plasmid-mediated, which allows for their widespread dissemination and outbreak-formation (particularly in Gram-negative bacteria; e.g., transmission of carbapenemase genes), while some bacteria possess intrinsic resistance mechanisms present in all species (e.g., resistance to tetracyclines, nitrofurantoin and polymyxin B in Proteus, Providencia and Morganella species) [17][18][19][20]. During susceptibility-testing and choosing the appropriate therapy, both clinicians and clinical microbiologists need to be aware of intrinsic resistance and local developments in acquired resistance levels [21].…”

Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment

“…Detection of CRE : In the recent past, several molecular genotyping methods such as microarrays, single and multiplex polymerase chain reaction (PCR) assays have been used to detect the common carbapenemases, including bla KPC , bla NDM , bla IMP , bla VIM and bla OXA-48 , in bacterial isolates or directly from clinical specimens [ 131 ]. However, these molecular methods can accurately detect specific carbapenemase genes but cannot detect novel carbapenemase genes.…”

Detection of New Delhi metallo-beta-lactamase enzyme gene bla NDM-1 associated with the Int-1 gene in Gram-negative bacteria collected from the effluent treatment plant of a tuberculosis care hospital in Delhi, India

“…Carbapenems (carbapenem, meropenem, imipenem) are currently our last option antimicrobial drugs in the battle against infections. Many times carbapenemase enzymeproducing Gram-negative bacteria are of superbug nature, wherein they are resistant to not only carbapenems but also to monobactums [1] and cephalosporins [2]. Many of the common nosocomial infectious agents, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, are now presenting as superbugs and lead to complicated, difficult-to-treat infections of the urinary tract, blood, brain, lungs and wounds [3][4][5][6][7].…”

“…NDM-1, 2, 3, 4 [14][15][16]) and the genes encoding them (bla NDM-1, 2, 3 ). Bacterial strains which are positive for bla NDM (genotypic resistance marker gene) and also produce NDM enzymes are particularly dangerous because, (1) There is no routine standard phenotypic test for MBL detection; (2) Consequently there is a possibility of high prevalence of unrecognized asymptomatic carriers amongst general population; (3) There is lack of effective antibiotics against NDM-1-positive superbugs; and (4) Plasmids from these bacteria can undergo wide rearrangement and thus can cause widespread horizontal transmission of the antibiotic resistance gene (bla NDM-1 ) [17][18][19][20].…”