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

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.