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      Expansion of KPC-producing Enterobacterales in four large hospitals in Hanoi, Vietnam

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          Highlights

          • 122 (20.4%) of 599 carbapenem-resistant Enterobacterales (CRE) isolates carried bla KPC genes .

          • Predominance of ST15 K. pneumoniae, whereas E. coli presented more diverse sequence types.

          • bla KPC-bearing plasmids were diverse in size.

          • Three different models of genetic context of bla KPC-2.

          • Hypothesis of circulation of resistant bacteria and transmission among hospitals.

          Abstract

          Objectives

          : The incidence of carbapenem resistance among nosocomial Gram-negative bacteria in Vietnam is high and increasing, including among Enterobacterales. In this study, we assessed the presence of one of the main carbapenemase genes, bla KPC, among carbapenem-resistant Enterobacterales (CRE) from four large hospitals in Hanoi, Vietnam, between 2010 and 2015, and described their key molecular characteristics.

          Methods

          : KPC-producing Enterobacterales were detected using conventional PCR and were further analysed using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting and whole-genome sequencing (WGS) for sequence typing and genetic characterisation.

          Results

          : bla KPC genes were detected in 122 (20.4%) of 599 CRE isolates. bla KPC-carrying plasmids were diverse in size. Klebsiella pneumoniae harbouring bla KPC genes belonged to ST15 and ST11, whereas KPC-producing Escherichia coli showed more diverse sequence types including ST3580, ST448, ST709 and ST405. Genotypic relationships supported the hypothesis of circulation of a population of ‘resident’ resistant bacteria in one hospital through the years and of transmission among these hospitals via patient transfer. WGS results revealed co-carriage of several other antimicrobial resistance genes and three different genetic contexts of bla KPC-2. Among these, the combination of IS Ecp1bla CTX-M and IS Kpn27bla KPC–ΔIS Kpn6 on the same plasmid is reported for the first time.

          Conclusion

          : We describe the dissemination of bla KPC-expressing Enterobacterales in four large hospitals in Hanoi, Vietnam, since 2010, which may have started earlier, along with their resistance patterns, sequence types, genotypic relationship, plasmid sizes and genetic context, thereby contributing to the overall picture of the antimicrobial resistance situation in Enterobacterales in Vietnam.

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          Most cited references30

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          IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era

          Abstract IQ-TREE (http://www.iqtree.org, last accessed February 6, 2020) is a user-friendly and widely used software package for phylogenetic inference using maximum likelihood. Since the release of version 1 in 2014, we have continuously expanded IQ-TREE to integrate a plethora of new models of sequence evolution and efficient computational approaches of phylogenetic inference to deal with genomic data. Here, we describe notable features of IQ-TREE version 2 and highlight the key advantages over other software.
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            Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications

            The PubMLST.org website hosts a collection of open-access, curated databases that integrate population sequence data with provenance and phenotype information for over 100 different microbial species and genera.  Although the PubMLST website was conceived as part of the development of the first multi-locus sequence typing (MLST) scheme in 1998 the software it uses, the Bacterial Isolate Genome Sequence database (BIGSdb, published in 2010), enables PubMLST to include all levels of sequence data, from single gene sequences up to and including complete, finished genomes.  Here we describe developments in the BIGSdb software made from publication to June 2018 and show how the platform realises microbial population genomics for a wide range of applications.  The system is based on the gene-by-gene analysis of microbial genomes, with each deposited sequence annotated and curated to identify the genes present and systematically catalogue their variation.  Originally intended as a means of characterising isolates with typing schemes, the synthesis of sequences and records of genetic variation with provenance and phenotype data permits highly scalable (whole genome sequence data for tens of thousands of isolates) means of addressing a wide range of functional questions, including: the prediction of antimicrobial resistance; likely cross-reactivity with vaccine antigens; and the functional activities of different variants that lead to key phenotypes.  There are no limitations to the number of sequences, genetic loci, allelic variants or schemes (combinations of loci) that can be included, enabling each database to represent an expanding catalogue of the genetic variation of the population in question.  In addition to providing web-accessible analyses and links to third-party analysis and visualisation tools, the BIGSdb software includes a RESTful application programming interface (API) that enables access to all the underlying data for third-party applications and data analysis pipelines.
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              The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes

              Whole-genome sequences are now available for many microbial species and clades, however existing whole-genome alignment methods are limited in their ability to perform sequence comparisons of multiple sequences simultaneously. Here we present the Harvest suite of core-genome alignment and visualization tools for the rapid and simultaneous analysis of thousands of intraspecific microbial strains. Harvest includes Parsnp, a fast core-genome multi-aligner, and Gingr, a dynamic visual platform. Together they provide interactive core-genome alignments, variant calls, recombination detection, and phylogenetic trees. Using simulated and real data we demonstrate that our approach exhibits unrivaled speed while maintaining the accuracy of existing methods. The Harvest suite is open-source and freely available from: http://github.com/marbl/harvest. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0524-x) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                J Glob Antimicrob Resist
                J Glob Antimicrob Resist
                Journal of Global Antimicrobial Resistance
                Published by Elsevier Ltd. on behalf of International Society of Chemotherapy for Infection and Cancer
                2213-7165
                2213-7173
                1 December 2021
                December 2021
                : 27
                : 200-211
                Affiliations
                [a ]National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
                [b ]National Institute of Infectious Diseases, Tokyo, Japan
                [c ]Institute of Tropical Diseases, Nagasaki University, Nagasaki, Japan
                [d ]Viet Duc Hospital, Hanoi, Vietnam
                [e ]Saint Paul Hospital, Hanoi, Vietnam
                [f ]Thanh Nhan Hospital, Hanoi, Vietnam
                [g ]108 Military Central Hospital, Hanoi, Vietnam
                [h ]Department of Medical Microbiology and Infectious Disease, Cardiff University, Cardiff, UK
                [i ]Oxford University Clinical Research Unit, Hanoi, Vietnam
                [j ]Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK
                [k ]MIVEGEC (IRD-CNRS-Université de Montpellier), Centre IRD, Montpellier, France
                [l ]Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
                [m ]Hanoi Medical University , Hanoi , Vietnam
                Author notes
                [* ]Corresponding author. National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hanoi 100 000, Vietnam. Tel.: +84 8 3426 9368. thh@ 123456nihe.org.vn
                [1]

                These two authors contributed equally to this work.

                Article
                S2213-7165(21)00213-7
                10.1016/j.jgar.2021.09.007
                8692232
                34607061
                b7fa0799-eff6-43e3-9adc-726042107025
                © 2021 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 December 2020
                : 30 August 2021
                : 14 September 2021
                Categories
                Article

                carbapenem resistance,kpc,enterobacterales,vietnam
                carbapenem resistance, kpc, enterobacterales, vietnam

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