Dissemination mechanisms of NDM genes in hospitalized patients

Abstract

Background NDM-producing Enterobacteriaceae are a major clinical concern worldwide. We characterized NDM-positive pathogens isolated from patients and assessed the dissemination patterns of the blaNDM genes in a hospital setting. Methods Eleven NDM-positive Enterobacteriaceae (three Enterobacter hormaechei, six Klebsiella pneumoniae and two Escherichia coli) were isolated from nine patients over a 1 year period. Antimicrobial susceptibility was assessed by MICs. A combination of short- and long-read WGS was used for genome analysis. Clinical treatment history of patients was linked with genetic features of individual isolates to investigate the dissemination patterns of the blaNDM genes and NDM-positive strains. Results bla NDM in clonal K. pneumoniae were transmitted between two patients. In other instances, an identical IncC plasmid encoding NDM-1 was transmitted between E. coli and K. pneumoniae isolated from the same patient, and an IncX3 plasmid, carrying blaNDM-1 or blaNDM-5, was harboured in non-clonal E. hormaechei. Varying patterns of IS elements were identified as a critical transmission mechanism in association with blaNDM genes. Conclusions Multiple transmission patterns were identified in hospitalized patients, including dissemination of clonal bacterial strains carrying resistance genes and horizontal transfer of resistance genes among divergent bacterial strains. Controlling spread of NDM is complex: while attention to standard infection control practices is critically important, this needs to be matched by aggressive efforts to limit unnecessary antimicrobial use, to minimize the selection for and risk of transfer of ‘high mobility’ resistance genes among Enterobacteriaceae.

Small-molecule inhibitors of bacterial-producing metallo-β-lactamases: insights into their resistance mechanisms and biochemical analyses of their activities

“…This can be accomplished through either gene mutation to bacterial chromosomal DNA 24 or horizontal resistance gene transfer. 25 In summary, the development of MDR by the well-known Gram-negative bacteria including K. pneumonia, A. baumannii, P. aeruginosa and Enterobacter species and some Gram-positive with which they constitute the ESKAPE pathogens, i.e., Enterococcus faecium and Staphylococcus aureus, are facilitated by multifaceted mechanisms, constituting treatment challenges. 26…”

“…12,50 Consequently, patients infected with this clinical strain of NDM frequently show a high chance of mortality. 25 The plasmid-encoded bla NDM gene, which is responsible for NDM enzymes, has been identified in water samples, and it is expected that this gene will spread across bacteria in the natural environment, 47 making its epidemiology alarming. The Enterobacteriaceae that are found to have the NDM include Klebsiella spp., Escherichia spp., and many more.…”

“…The Enterobacteriaceae that are found to have the NDM include Klebsiella spp., Escherichia spp., and many more. 25,50 In recognizing their global threats, they are categorised under the WHO critical pathogens list (Priority 1) as bacteria that mostly produce NDM BLs. 66…”

Use of whole genomic sequencing to detect New Delhi metallo-B-lactamase (NDM)-producing Escherichia coli outbreak associated with endoscopic procedures

“…1 In less than a decade since NDM was first described in 2009, it was declared an urgent global threat in 2019 by the Centers for Disease Control and Prevention. 2 These bacteria possess significant antimicrobial resistance (AMR), and early detection of an outbreak is difficult. 3 Containment involves implementation of strict infection control measures, 4 and prior outbreaks have been associated with lapses in infection control in long-term acute care and skilled nursing facilities, 5 endoscopic procedures, 6 and contaminated total parenteral nutrition.…”

Novel Megaplasmid Driving NDM-1-Mediated Carbapenem Resistance in Klebsiella pneumoniae ST1588 in South America

“…Worryingly, infections produced by NDM-producers are associated with high mortality rates, representing an important challenge for public health [ 5 ]. Among NDM carbapenemases, NDM-1 has been identified in several Gram-negative pathogens, including Enterobacterales and non-fermenting rods recovered in different geographical areas, from human and animal hosts and environmental sources [ 5 , 6 ].…”