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Dissemination mechanisms of NDM genes in hospitalized patients
Yuting Zhai1,2, Shinyoung Lee1,2, Lin Teng1,2
1Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
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 bla NDM 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 bla NDM 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 bla NDM-1 or bla NDM-5, was harboured in non-clonal E. hormaechei. Varying patterns of IS elements were identified as a critical transmission mechanism in association with bla NDM 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.
Insights
NDM-producing Enterobacteriaceae spread through clonal strains and horizontal gene transfer in hospitals. Controlling NDM requires infection control and reduced antimicrobial use to limit high-mobility resistance gene transfer.
Area of Science:
- Clinical Microbiology
- Genetics
- Infectious Diseases
Background:
- New Delhi Metallo-beta-lactamase (NDM)-producing Enterobacteriaceae pose a significant global health threat.
- Characterization of NDM-positive pathogens and their dissemination is crucial for effective control.
Purpose of the Study:
- To investigate the transmission patterns of NDM-producing Enterobacteriaceae in a hospital setting.
- To analyze the genetic mechanisms underlying the spread of blaNDM genes.
Main Methods:
- Isolation and identification of NDM-positive Enterobacteriaceae from patients.
- Antimicrobial susceptibility testing using MICs.
- Whole Genome Sequencing (WGS) using short and long reads.
- Linking clinical data with isolate genetic features.
Main Results:
- Identified transmission of blaNDM in clonal Klebsiella pneumoniae between patients.
- Demonstrated horizontal plasmid transfer (IncC and IncX3) encoding NDM-1/NDM-5 between different Enterobacteriaceae species (E. coli, K. pneumoniae, E. hormaechei).
- Highlighted the role of insertion sequence (IS) elements in blaNDM gene transmission.
Conclusions:
- Multiple transmission routes for NDM-producing Enterobacteriaceae exist, including clonal spread and horizontal gene transfer.
- Controlling NDM requires integrated strategies: robust infection control and judicious antimicrobial stewardship.
- Minimizing antimicrobial use is essential to reduce selection pressure for high-mobility resistance genes.
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