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Dissemination Mechanisms of New Delhi Metallo-β-lactamase Genes in Hospitalized Patients

31 Pages Posted: 19 Oct 2020

See all articles by Yuting Zhai

Yuting Zhai

University of Florida - Emerging Pathogens Institute

Shinyoung Lee

University of Florida - Emerging Pathogens Institute

Lin Teng

University of Florida - Institute of Food and Agricultural Sciences (IFAS), Department of Animal Sciences

Zhengxin Ma

University of Florida - Institute of Food and Agricultural Sciences (IFAS), Department of Animal Sciences

Nicole B. Hilliard

University of Florida Health/Shands Hospital - Infection Control

Robert J. May

University of Florida Health/Shands Hospital - Infection Control

Scott A. Brown

University of Florida Health/Shands Hospital - Infection Control

Fahong Yu

University of Florida Health/Shands Hospital - Infection Control

Kathryn E. DeSear

University of Florida Health/Shands Hospital - Department of Pharmacy

Kartikeya Cherabuddi

University of Florida - Division of Infectious Diseases and Global Medicine

Kenneth H. Rand

University of Florida - Division of Infectious Diseases and Global Medicine

J. Glenn Morris Jr.

University of Florida - Emerging Pathogens Institute

Nicole M. Iovine

University of Florida Health/Shands Hospital - Infection Control

KwangCheol Casey Jeong

University of Florida - Emerging Pathogens Institute

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Abstract

Background: New Delhi metallo-β-lactamase (NDM) producing Enterobacteriaceae is 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 one-year period. Antimicrobial susceptibility was assessed by minimum inhibitory concentrations. A combination of short- and long-read whole genome sequencing 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.

Findings: blaNDM 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 the same IncX3 plasmid, carrying blaNDM-1 or blaNDM-5, was harbored in E. hormaechei. Varying patterns of insertion sequence (IS) elements were identified as a critical transmission mechanism in association with blaNDM genes.

Interpretation: 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.

Funding Statement: This project is part of the University of Florida’s “Creating the Healthiest Generation” Moonshot initiative, which is supported by the UF Office of the Provost, UF Office of Research, UF Health, UF College of Medicine, and UF Clinical and Translational Science Institute.

Declaration of Interests: KC reports grants from Arrow International, Inc. and National Institute of Health - Antibiotic Research Leadership Group and personal fees from BioFire diagnostics for travel and speaker. All other authors declare no competing interests.

Ethics Approval Statement: IRB-approved study at the University of Florida.

Keywords: New Delhi metallo-β-lactamase, Carbapenemase, mobile genetic elements, Whole genome sequencing

Suggested Citation

Zhai, Yuting and Lee, Shinyoung and Teng, Lin and Ma, Zhengxin and Hilliard, Nicole B. and May, Robert J. and Brown, Scott A. and Yu, Fahong and DeSear, Kathryn E. and Cherabuddi, Kartikeya and Rand, Kenneth H. and Morris Jr., J. Glenn and Iovine, Nicole M. and Jeong, KwangCheol Casey, Dissemination Mechanisms of New Delhi Metallo-β-lactamase Genes in Hospitalized Patients. Available at SSRN: https://ssrn.com/abstract=3710625 or http://dx.doi.org/10.2139/ssrn.3710625

Yuting Zhai

University of Florida - Emerging Pathogens Institute ( email )

Gainesville, FL
United States

Shinyoung Lee

University of Florida - Emerging Pathogens Institute ( email )

Gainesville, FL
United States

Lin Teng

University of Florida - Institute of Food and Agricultural Sciences (IFAS), Department of Animal Sciences

Gainesville, FL
United States

Zhengxin Ma

University of Florida - Institute of Food and Agricultural Sciences (IFAS), Department of Animal Sciences

Gainesville, FL
United States

Nicole B. Hilliard

University of Florida Health/Shands Hospital - Infection Control

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Robert J. May

University of Florida Health/Shands Hospital - Infection Control

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Scott A. Brown

University of Florida Health/Shands Hospital - Infection Control

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Fahong Yu

University of Florida Health/Shands Hospital - Infection Control ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Kathryn E. DeSear

University of Florida Health/Shands Hospital - Department of Pharmacy ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Kartikeya Cherabuddi

University of Florida - Division of Infectious Diseases and Global Medicine ( email )

2055 Mowry Road
P.O. Box 103600
Gainesville, FL 32610
United States

Kenneth H. Rand

University of Florida - Division of Infectious Diseases and Global Medicine ( email )

2055 Mowry Road
P.O. Box 103600
Gainesville, FL 32610
United States

J. Glenn Morris Jr.

University of Florida - Emerging Pathogens Institute ( email )

Gainesville, FL
United States

Nicole M. Iovine

University of Florida Health/Shands Hospital - Infection Control ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

KwangCheol Casey Jeong (Contact Author)

University of Florida - Emerging Pathogens Institute ( email )

Gainesville, FL
United States