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      Clostridium difficile infection: review

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          Abstract

          Clostridium difficile ( C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.

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          Most cited references76

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          Bile acids: regulation of synthesis.

          Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and energy metabolism. The enterohepatic circulation of bile acids exerts important physiological functions not only in feedback inhibition of bile acid synthesis but also in control of whole-body lipid homeostasis. In the liver, bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces an atypical nuclear receptor small heterodimer partner, which subsequently inhibits nuclear receptors, liver-related homolog-1, and hepatocyte nuclear factor 4alpha and results in inhibiting transcription of the critical regulatory gene in bile acid synthesis, cholesterol 7alpha-hydroxylase (CYP7A1). In the intestine, FXR induces an intestinal hormone, fibroblast growth factor 15 (FGF15; or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signaling to inhibit bile acid synthesis. However, the mechanism by which FXR/FGF19/FGFR4 signaling inhibits CYP7A1 remains unknown. Bile acids are able to induce FGF19 in human hepatocytes, and the FGF19 autocrine pathway may exist in the human livers. Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome.
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            Clostridium difficile infection

            Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.
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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.).

                Author and article information

                Contributors
                04812 - 424 73 49 , jacek.czepiel@uj.edu.pl
                gbiesiada@op.pl
                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
                3 April 2019
                3 April 2019
                2019
                : 38
                : 7
                : 1211-1221
                Affiliations
                [1 ]ISNI 0000 0001 2162 9631, GRID grid.5522.0, Department of Infectious and Tropical Diseases, Jagiellonian University, , Medical College, ; Śniadeckich 5, 31-501 Krakow, Poland
                [2 ]Saint Ann’s Hospital, Miechów, Poland
                [3 ]ISNI 0000000113287408, GRID grid.13339.3b, Department of Medical Microbiology, , Medical University of Warsaw, ; Warsaw, Poland
                [4 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Medical Microbiology, Centre for Infectious Diseases, , Leiden University Medical Center, ; Leiden, The Netherlands
                [5 ]ISNI 0000 0001 2208 0118, GRID grid.31147.30, Centre for Infectious Diseases Research, Diagnostics and Laboratory Surveillance, RIVM, ; Bilthoven, The Netherlands
                [6 ]ISNI 0000 0001 0860 4915, GRID grid.63054.34, Department of Medicine, John Dempsey Hospital, , University of Connecticut, ; Farmington, CT USA
                [7 ]ISNI 0000 0001 1216 0093, GRID grid.412700.0, University Hospital, ; Krakow, Poland
                Author information
                http://orcid.org/0000-0002-9997-8417
                Article
                3539
                10.1007/s10096-019-03539-6
                6570665
                30945014
                e5fe486d-8a68-4228-b87f-6be55749b142
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 27 January 2019
                : 12 March 2019
                Funding
                Funded by: Jagiellonian University in Krakow
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Infectious disease & Microbiology
                antibiotic-associated diarrhea,clostridium difficile,diagnosis,fecal transplantation,treatment

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