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      Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

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          Abstract

          Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

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          Most cited references119

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          Hypervirulent (hypermucoviscous) Klebsiella pneumoniae

          A new hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae has emerged. First described in the Asian Pacific Rim, it now increasingly recognized in Western countries. Defining clinical features are the ability to cause serious, life-threatening community-acquired infection in younger healthy hosts, including liver abscess, pneumonia, meningitis and endophthalmitis and the ability to metastatically spread, an unusual feature for enteric Gram-negative bacilli in the non-immunocompromised. Despite infecting a healthier population, significant morbidity and mortality occurs. Although epidemiologic features are still being defined, colonization, particularly intestinal colonization, appears to be a critical step leading to infection. However the route of entry remains unclear. The majority of cases described to date are in Asians, raising the issue of a genetic predisposition vs. geospecific strain acquisition. The traits that enhance its virulence when compared with “classical” K. pneumoniae are the ability to more efficiently acquire iron and perhaps an increase in capsule production, which confers the hypermucoviscous phenotype. An objective diagnostic test suitable for routine use in the clinical microbiology laboratory is needed. If/when these strains become increasingly resistant to antimicrobials, we will be faced with a frightening clinical scenario.
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            Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention.

            Over the past 10 years, dissemination of Klebsiella pneumoniae carbapenemase (KPC) has led to an increase in the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. In the previous year, other carbapenemase subtypes, including New Delhi metallo-β-lactamase, have been identified among Enterobacteriaceae in the United States. Like KPC, these enzymes are frequently found on mobile genetic elements and have the potential to spread widely. As a result, preventing both CRE transmission and CRE infections have become important public health objectives. This review describes the current epidemiology of CRE in the United States and highlights important prevention strategies. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
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              Klebsiella pneumoniae liver abscess: a new invasive syndrome.

              Klebsiella pneumoniae is a well known human nosocomial pathogen. Most community-acquired K pneumoniae infections cause pneumonia or urinary tract infections. During the past two decades, however, a distinct invasive syndrome that causes liver abscesses has been increasingly reported in Asia, and this syndrome is emerging as a global disease. In this Review, we summarise the clinical presentation and management as well the microbiological aspects of this invasive disease. Diabetes mellitus and two specific capsular types in the bacterium predispose a patient to the development of liver abscesses and the following metastatic complications: bacteraemia, meningitis, endophthalmitis, and necrotising fasciitis. For patients with this invasive syndrome, appropriate antimicrobial treatment combined with percutaneous drainage of liver abscesses increases their chances of survival. Rapid detection of the hypervirulent strain that causes this syndrome allows earlier diagnosis and treatment, thus minimising the occurrence of sequelae and improving clinical outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                21 November 2017
                2017
                : 7
                : 483
                Affiliations
                [1] 1National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University , Yongin, South Korea
                [2] 2Biotechnology Program, North Shore Community College , Danvers, MA, United States
                [3] 3Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University , Anseong, South Korea
                Author notes

                Edited by: Kelly L. Wyres, University of Melbourne, Australia

                Reviewed by: Russel Lee, National University of Singapore, Singapore; Xingmin Sun, University of South Florida, United States; Scott Wesley Long, Houston Methodist Hospital, United States

                *Correspondence: Sang Hee Lee sangheelee@ 123456mju.ac.kr

                †These authors have contributed equally to this work.

                Article
                10.3389/fcimb.2017.00483
                5702448
                29209595
                4dd4d996-c161-4258-acfd-f65d3425110e
                Copyright © 2017 Lee, Lee, Park, Jeon, Kim, Cha, Jeong and Lee.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 July 2017
                : 09 November 2017
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 128, Pages: 13, Words: 11917
                Funding
                Funded by: Ministry of Science, ICT and Future Planning 10.13039/501100003621
                Award ID: NRF-2017R1A2B4002315
                Funded by: Korea Centers for Disease Control & Prevention 10.13039/501100003669
                Award ID: 2017N-ER5404-00
                Funded by: National Research Foundation of Korea 10.13039/501100002701
                Award ID: NRF-2017M3A9E4078014
                Award ID: NRF-2017M3A9E4078017
                Categories
                Microbiology
                Review

                Infectious disease & Microbiology
                antimicrobial resistance,hypervirulent klebsiella pneumoniae,epidemiology,resistance mechanism,serotype,sequence type

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