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      Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients

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          Summary

          Klebsiella pneumoniae colonization is a significant risk factor for infection in ICU, with approximately half of K. pneumoniae infections resulting from patients’ own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.

          Abstract

          Background.

          Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized.

          Methods.

          We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events.

          Results.

          Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%–8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%–51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients’ own unique strain, and 48% of screened patients with infections were positive for prior colonization.

          Conclusions.

          These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients’ own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.

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          Most cited references23

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          Genome-scale rates of evolutionary change in bacteria

          Estimating the rates at which bacterial genomes evolve is critical to understanding major evolutionary and ecological processes such as disease emergence, long-term host–pathogen associations and short-term transmission patterns. The surge in bacterial genomic data sets provides a new opportunity to estimate these rates and reveal the factors that shape bacterial evolutionary dynamics. For many organisms estimates of evolutionary rate display an inverse association with the time-scale over which the data are sampled. However, this relationship remains unexplored in bacteria due to the difficulty in estimating genome-wide evolutionary rates, which are impacted by the extent of temporal structure in the data and the prevalence of recombination. We collected 36 whole genome sequence data sets from 16 species of bacterial pathogens to systematically estimate and compare their evolutionary rates and assess the extent of temporal structure in the absence of recombination. The majority (28/36) of data sets possessed sufficient clock-like structure to robustly estimate evolutionary rates. However, in some species reliable estimates were not possible even with ‘ancient DNA’ data sampled over many centuries, suggesting that they evolve very slowly or that they display extensive rate variation among lineages. The robustly estimated evolutionary rates spanned several orders of magnitude, from approximately 10−5 to 10−8 nucleotide substitutions per site year−1. This variation was negatively associated with sampling time, with this relationship best described by an exponential decay curve. To avoid potential estimation biases, such time-dependency should be considered when inferring evolutionary time-scales in bacteria.
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            Molecular Epidemiology of Colonizing and Infecting Isolates of Klebsiella pneumoniae

            K. pneumoniae commonly infects hospitalized patients, and these infections are increasingly resistant to carbapenems, the antibiotics of last resort for life-threatening bacterial infections. To prevent and treat these infections, we must better understand how K. pneumoniae causes disease and discover new ways to predict and detect infections. This study demonstrates that colonization with K. pneumoniae in the intestinal tract is strongly linked to subsequent infection. This finding helps to identify a potential time frame and possible approach for intervention: the colonizing strain from a patient could be isolated as part of a risk assessment, and antibiotic susceptibility testing could guide empirical therapy if the patient becomes acutely ill.
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              Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting.

              Infections attributable to vancomycin-resistant Enterococcus (VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 July 2017
                24 March 2017
                24 March 2017
                : 65
                : 2
                : 208-215
                Affiliations
                [1 ] Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute and
                [2 ] Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne , and
                [3 ] Microbiology Unit, Alfred Health , Melbourne, Victoria, Australia;
                [4 ] Wellcome Trust Sanger Institute , Hinxton, Cambridgeshire, United Kingdom;
                [5 ] Infectious Diseases Clinical Research Unit and
                [6 ] Intensive Care Unit, The Alfred Hospital ,
                [7 ] Australian and New Zealand Intensive Care – Research Centre, School of Public Health and Preventive Medicine, Monash University , and
                [8 ] Microbiology Unit & Department of Infectious Diseases, The Alfred Hospital , Melbourne, Victoria, Australia
                Author notes

                Correspondence: K. E. Holt, Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia ( kholt@ 123456unimelb.edu.au ).

                Article
                cix270
                10.1093/cid/cix270
                5850561
                28369261
                6ec149b0-4ffd-4717-ab34-89f213bfd433
                © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 January 2017
                : 21 March 2017
                Page count
                Pages: 8
                Funding
                Funded by: Wellcome Trust 10.13039/100004440
                Funded by: National Health and Medical Research Council of Australia
                Award ID: 1043822
                Award ID: 1061409
                Funded by: Australian Government Research Training Program
                Categories
                Major Article

                Infectious disease & Microbiology
                klebsiella pneumoniae,gastrointestinal colonization,genomic epidemiology,intensive care,hospital acquired infection.

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