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      Longitudinal investigation of carriage rates and genotypes of toxigenic Clostridium difficile in hepatic cirrhosis patients

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          Abstract

          Toxigenic Clostridium difficile ( C. difficile) carriers represent an important source in the transmission of C. difficile infection (CDI) during hospitalisation, but its prevalence and mode in patients with hepatic cirrhosis are not well established. We investigated longitudinal changes in carriage rates and strain types of toxigenic C. difficile from admission to discharge among hepatic cirrhosis patients. Toxigenic C. difficile was detected in 104 (19.8%) of 526 hepatic cirrhosis patients on admission, and the carriage status changed in a portion of patients during hospitalisation. Approximately 56% (58/104) of patients lost the colonisation during their hospital stay. Among the remaining 48 patients who remained positive for toxigenic C. difficile, the numbers of patients who were positive at one, two, three and four isolations were 10 (55.6%), three (16.7%), two (11.1%) and three (16.7%), respectively. Twenty-eight patients retained a particular monophyletic strain at multiple isolations. The genotype most frequently identified was the same as that frequently identified in symptomatic CDI patients. A total of 25% (26/104) of patients were diagnosed with CDI during their hospital stay. Conclusions: Colonisation with toxigenic C. difficile strains occurs frequently in cirrhosis patients and is a risk factor for CDI.

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          Most cited references28

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          Host and pathogen factors for Clostridium difficile infection and colonization.

          Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).
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            Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile.

            In addition to the two large clostridial cytotoxins (TcdA and TcdB) certain strains of Clostridium difficile produce an actin-specific ADP-ribosyltransferase, or binary toxin. PCR reactions were developed to detect genes encoding the enzymatic (cdtA) and binding (cdtB) components of the binary toxin and 170 representative strains were tested to assess the prevalence of the toxin. Positive PCR results (n=59) were confirmed by immunoblotting and ADP-ribosyltransferase assay. PCR ribotype and toxinotype (restriction fragment length polymorphism analysis of genes for TcdA and TcdB) correlated with possession of binary toxin genes. All strains with cdtA and cdtB belonged to toxin-variable toxinotypes and five toxin-producing groups of strains have been described according to the presence or absence of TcdA, TcdB and binary toxin. Result indicate that ca. 6.4% of toxigenic isolates of C. difficile referred to the Anaerobe Reference Unit from UK hospitals have cdtA and cdtB genes.
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              Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis.

              It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied.
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                Author and article information

                Journal
                Epidemiol Infect
                Epidemiol. Infect
                HYG
                Epidemiology and Infection
                Cambridge University Press (Cambridge, UK )
                0950-2688
                1469-4409
                2019
                28 March 2019
                : 147
                : e166
                Affiliations
                [1 ]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, Zhejiang, China
                [2 ]Clinical Laboratory, Hangzhou Third Hospital , Hangzhou, Zhejiang, China
                [3 ]Medical Engineering Department, The First Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, Zhejiang, China
                [4 ]Women's Hospital, School of Medicine, Zhejiang University , Hangzhou, Zhejiang, China
                Author notes
                Author for correspondence: Lanjuan Li, E-mail: ljli@ 123456zju.edu.cn
                [*]

                Yunbo Chen and Hongqin Qu contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-6945-0593
                Article
                S0950268819000554 00055
                10.1017/S0950268819000554
                6518478
                31063095
                e3b53528-6b06-4313-b280-80de9809af05
                © The Author(s) 2019

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

                History
                : 24 January 2018
                : 30 October 2018
                : 26 February 2019
                Page count
                Figures: 1, Tables: 1, References: 35, Pages: 8
                Categories
                Original Paper

                Public health
                carriage,clostridium difficile,genotype
                Public health
                carriage, clostridium difficile, genotype

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