Resistome and virulome accretion in an NDM-1-producing ST147 sublineage of Klebsiella pneumoniae associated with an outbreak in Tuscany, Italy: a genotypic and phenotypic characterisation.

BACKGROUND

Carbapenemase-producing Enterobacterales (CPE), particularly those producing metallo-β-lactamases, are among the most challenging antibiotic-resistant pathogens, causing outbreaks of difficult-to-treat nosocomial infections worldwide. Since November 2018, an outbreak of New Delhi metallo-β-lactamases-positive CPE (NDM-CPE) has emerged in Tuscany, Italy. In this study, we aimed to investigate the NDM-CPE associated with the outbreak and characterise the responsible Klebsiella pneumoniae clone.

METHODS

We used whole-genome sequencing and bioinformatic analysis to characterise NDM-CPE isolates that caused bloodstream infections in 53 patients at 11 hospitals in Tuscany and that were collected between Jan 1, 2018, and July 5, 2019 (ie, the early phase of the outbreak and preceding months). The CPE isolates characterised in this study were isolated and identified at the species level and as NDM producers by six diagnostic microbiology laboratories that serve the 11 hospitals. We used comparative genomic analysis, antimicrobial susceptibility testing, plasmid conjugal transfer assays, evaluation of virulence potential in the Galleria mellonella infection model, and serum bactericidal assays to further characterise the clone causing the outbreak.

FINDINGS

The outbreak was sustained by an ST147 K pneumoniae producing NDM-1, which had a complex resistome that mediated resistance to most antimicrobials (except cefiderocol, the aztreonam-avibactam combination, colistin, and fosfomycin). The clone belonged to a sublineage of probably recent evolution, occurred by the sequential acquisition of an integrative and conjugative element encoding the yersiniabactin siderophore, an FIB(pQil)-type multiresistance plasmid carrying bla

INTERPRETATION

This description of a sublineage of ST147 K pneumoniae with a complex resistome and virulome that is capable of sustaining a large regional outbreak adds to existing research on the evolutionary trajectories within high-risk clones of K pneumoniae. Global surveillance programmes are warranted to track the dissemination of these lineages, and to prevent and control their spread.

FUNDING

Italian Ministry of Health and Department of Experimental and Clinical Medicine, University of Florence.

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests GMR reports grants, personal fees, and non-financial support from Accelerate Diagnostics, personal fees from Becton Dickinson, Zambon, Roche, Thermo Fisher, QPex, Qiagen, and Pfizer, grants and personal fees from bioMérieux, Cepheid, MSD, Shionogi, Beckman Coulter, Menarini, Angelini Pharma, and Nordic Pharma, grants from Seegene, Arrow, Symcel, Hain Lifescience, Meridian, SetLance, Qvella, Qlinea, Biomedical Service, Quidel, and DID, and personal fees and fees for bacterial strains from Venatorx, outside the submitted work. TG reports personal fees from Alifax, bioMérieux, Thermo Fisher Scientific, Seegene, Accelerate Diagnostics, and VenatorX, and grants from AstraZeneca, outside the submitted work. AA reports personal fees from Seegene, Menarini, Arrow Diagnostic, and Accelerate Diagnostic, and non-financial support from SymCel, outside the submitted work. IB reports non-financial support from Diesse Diagnostica Senese, outside the submitted work. All other authors declare no competing interests.