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      Molecular epidemiology of carbapenemase-producing Enterobacterales in Finland, 2012–2018

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          Abstract

          Carbapenemase-producing Enterobacterales (CPE) pose an increasing threat to patient safety and healthcare systems globally. We present molecular epidemiology of CPE in Finland during 2012–2018 with detailed characteristics of CPE strains causing clusters during the same time period. All Finnish clinical microbiology laboratories send Enterobacterales isolates with reduced susceptibility to carbapenems or isolates producing carbapenemase to the reference laboratory for further characterization by whole genome sequencing (WGS). In total, 231 CPE strains from 202 patients were identified during 2012–2018. Of the strains, 59% were found by screening and 32% from clinical specimens, the latter were most commonly urine. Travel and/or hospitalization history abroad was reported for 108/171 strains (63%). The most common species were Klebsiella pneumoniae (45%), Escherichia coli (40%), and Citrobacter freundii (6%), and the most common carbapenemase genes bla NDM-like (35%), bla OXA-48-like (33%), and bla KPC-like (31%). During 2012–2018, the annual number of CPE strains increased from 9 to 70 and different sequence types from 7 to 33, and bla OXA-48-like genes became the most prevalent. Of the clusters, 3/8 were linked to traveling or hospitalization abroad and 5/8 were caused by K. pneumoniae clone clonal complex 258. Most of the clusters were caused by K. pneumoniae producing KPC. High variety among different sequence types indicates that majority of CPE cases detected in Finland are likely imported from foreign countries. Nearly one-third of the cases are not found by screening suggesting that there is hidden transmission occurring in the healthcare settings.

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          The online version of this article (10.1007/s10096-020-03885-w) contains supplementary material, which is available to authorized users.

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          Most cited references14

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          Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance.

          The management of infections due to Klebsiella pneumoniae has been complicated by the emergence of antimicrobial resistance, especially to carbapenems. Resistance to carbapenems in K. pneumoniae involves multiple mechanisms, including the production of carbapenemases (e.g., KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins and the upregulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of β-lactamases (e.g., AmpC). K. pneumoniae sequence type 258 (ST258) emerged during the early to mid-2000s as an important human pathogen and has spread extensively throughout the world. ST258 comprises two distinct lineages, namely, clades I and II, and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatibility group F plasmids with blaKPC have contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producing K. pneumoniae remains unknown. Some newer agents show promise for treating infections due to KPC producers; however, effective options for the treatment of NDM producers remain elusive.
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            Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study.

            Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals.
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              Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence.

              We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.
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                Author and article information

                Contributors
                kati.raisanen@thl.fi
                Journal
                Eur J Clin Microbiol Infect Dis
                Eur. J. Clin. Microbiol. Infect. Dis
                European Journal of Clinical Microbiology & Infectious Diseases
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0934-9723
                1435-4373
                19 April 2020
                19 April 2020
                2020
                : 39
                : 9
                : 1651-1656
                Affiliations
                [1 ]Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
                [2 ]NordLab, Oulu, Finland
                [3 ]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Clinical Microbiology, , University of Helsinki, ; Helsinki, Finland
                [4 ]GRID grid.15485.3d, ISNI 0000 0000 9950 5666, Helsinki University Hospital, ; Helsinki, Finland
                [5 ]GRID grid.410552.7, ISNI 0000 0004 0628 215X, Department of Clinical Microbiology, , Turku University Hospital, ; Turku, Finland
                [6 ]Department of Microbiology, Fimlab Laboratories Ltd., Tampere, Finland
                Article
                3885
                10.1007/s10096-020-03885-w
                7427707
                32307627
                e8659279-61d1-4dda-8e48-f39aa6cd3cd3
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 February 2020
                : 30 March 2020
                Funding
                Funded by: National Institute for Health and Welfare (THL)
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Infectious disease & Microbiology
                cpe,enterobacterales,finland,whole genome sequencing,molecular epidemiology

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