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      2019 update of the WSES guidelines for management of Clostridioides ( Clostridium) difficile infection in surgical patients

      review-article
      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 8 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 11 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 53 , 66 , 67 , 68 , 69 , 1 , 70 , 71 , 72 , 73 , 74
      World Journal of Emergency Surgery : WJES
      BioMed Central
      Clostridioides difficile infection, Clostridium difficile infection, Pseudomembranous colitis, Antimicrobial treatment, Fecal microbiota transplantation, Infection control, Antimicrobial stewardship

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          Abstract

          In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

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          Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.

          Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.
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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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              Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe.

              Toxins A and B are the primary virulence factors of Clostridium difficile. Since 2002, an epidemic of C difficile-associated disease with increased morbidity and mortality has been present in Quebec province, Canada. We characterised the dominant strain of this epidemic to determine whether it produces higher amounts of toxins A and B than those produced by non-epidemic strains. We obtained isolates from 124 patients from Centre Hospitalier Universitaire de Sherbrooke in Quebec. Additional isolates from the USA, Canada, and the UK were included to increase the genetic diversity of the toxinotypes tested. Isolate characterisation included toxinotyping, pulsed-field gel electrophoresis (PFGE), PCR ribotyping, detection of a binary toxin gene, and detection of deletions in a putative negative regulator for toxins A and B (tcdC). By use of an enzyme-linked immunoassay, we measured the in-vitro production of toxins A and B by epidemic strain and non-dominant strain isolates. The epidemic strain was characterised as toxinotype III, North American PFGE type 1, and PCR-ribotype 027 (NAP1/027). This strain carried the binary toxin gene cdtB and an 18-bp deletion in tcdC. We isolated this strain from 72 patients with C difficile-associated disease (58 [67%] of 86 with health-care-associated disease; 14 [37%] of 38 with community-acquired disease). Peak median (IQR) toxin A and toxin B concentrations produced in vitro by NAP1/027 were 16 and 23 times higher, respectively, than those measured in isolates representing 12 different PFGE types, known as toxinotype 0 (toxin A, median 848 microg/L [IQR 504-1022] vs 54 microg/L [23-203]; toxin B, 180 microg/L [137-210] vs 8 microg/L [5-25]; p<0.0001 for both toxins). The severity of C difficile-associated disease caused by NAP1/027 could result from hyperproduction of toxins A and B. Dissemination of this strain in North America and Europe could lead to important changes in the epidemiology of C difficile-associated disease.
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                Author and article information

                Contributors
                massimosartelli@gmail.com
                stefano932@gmail.com
                mcfarland.lynne.v@gmail.com
                khanna.sahil@mayo.edu
                Luis.Furuya-Kanamori@anu.edu.au
                nadirabuzeid@gmail.com
                fabuzidan@uaeu.ac.ae
                aiace63@gmail.com
                augustin.goran@gmail.com
                Rbalam@hadassah.org.il
                o_ben-ishay@rambam.health.gov.il
                walt@biffl.com
                Stephen.Brecher@va.gov
                acamacho_md@yahoo.com
                miguelangel.cainzos@usc.es
                shirley.chan@talk21.com
                jillcher@med.umich.edu
                jclanton82@gmail.com
                federico.coccolini@gmail.com
                maria_elenacocuz@yahoo.com
                raulcoimbra62@yahoo.com
                francescocortese@gmail.com
                yunfengcuidoctor@aliyun.com
                czepiel.jacek1@gmail.com
                zdemetr@yahoo.com
                idicarlo@unict.it
                salo75@inwind.it
                dumitrui@hotmail.com
                Christian.Eckmann@klinikum-peine.de
                eheiland@vitalcareinc.com
                JDForrester84@gmail.com
                Jean-Louis.Frossard@hcuge.ch
                fragagp2008@gmail.com
                dfry@consultmpa.com
                ritagaleiras@hotmail.es
                wghnnam@gmail.com
                caxiaogomes@gmail.com
                Ewen.Griffiths@uhb.nhs.uk
                xguirao@gmail.com
                Mohamed.Hassan-Ahmed@mkhospital.nhs.uk
                t.herzog@klinikum-bochum.de
                erythrokim@paik.ac.kr
                Tariq.Iqbal@uhb.nhs.uk
                kararda@yahoo.com
                Kamal.Itani@va.gov
                labricciosafrancesco@gmail.com
                justnleeyy@gmail.com
                Paul.Juang@stlcop.edu
                alekara@sbb.rs
                kim.peter.p01@gmail.com
                y_kluger@rambam.health.gov.il
                Ari.Leppaniemi@hus.fi
                bolloon@hotmail.com
                gmmachain@yahoo.com
                drsanjay.marwah@gmail.com
                mazuskij@wudosis.wustl.edu
                gokhanmetan@gmail.com
                ernest.moore@dhha.org
                frederick.moore@surgery.ufl.edu
                ordonezcarlosa@gmail.com
                lpagani.ID@gmail.com
                nicola.petrosillo@inmi.it
                fasportela@gmail.com
                kemrasa@gmail.com
                miran.rems@sb-je.si
                bsakakushev@gmail.com
                hhaassll@gmail.com
                gsganga@tiscali.it
                vgshelat@rediffmail.com
                patrizia.spigaglia@iss.it
                pierre.tattevin@chu-rennes.fr
                trana.cristian@gmail.com
                libor.urbanek@fnusa.cz
                Jan.Ulrych@vfn.cz
                pierluigi.viale@unibo.it
                gianluca.baiocchi@unibs.it
                faustocatena@gmail.com
                Journal
                World J Emerg Surg
                World J Emerg Surg
                World Journal of Emergency Surgery : WJES
                BioMed Central (London )
                1749-7922
                28 February 2019
                28 February 2019
                2019
                : 14
                : 8
                Affiliations
                [1 ]Department of Surgery, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
                [2 ]ISNI 0000000459364044, GRID grid.460062.6, Infectious Diseases Department, , Trieste University Hospital, ; Trieste, Italy
                [3 ]ISNI 0000000122986657, GRID grid.34477.33, Medicinal Chemistry, School of Pharmacy, , University of Washington, ; Seattle, WA USA
                [4 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Gastroenterology and Hepatology, Department of Medicine, , Mayo Clinic, ; Rochester, MN USA
                [5 ]ISNI 0000 0001 2180 7477, GRID grid.1001.0, Research School of Population Health, , Australian National University, ; Acton, ACT Australia
                [6 ]GRID grid.442422.6, Department of Microbiology, Faculty of Medical Laboratory Sciences, , Omdurman Islamic University, ; Khartoum, Sudan
                [7 ]ISNI 0000 0001 2193 6666, GRID grid.43519.3a, Department of Surgery, College of Medicine and Health Sciences, , UAE University, ; Al-Ain, United Arab Emirates
                [8 ]ISNI 0000 0004 1758 8744, GRID grid.414682.d, Department of General Surgery, , Bufalini Hospital, ; Cesena, Italy
                [9 ]ISNI 0000 0001 0657 4636, GRID grid.4808.4, Department of Surgery, University Hospital Centre Zagreb and School of Medicine, , University of Zagreb, ; Zagreb, Croatia
                [10 ]ISNI 0000 0001 2221 2926, GRID grid.17788.31, Trauma and Acute Care Surgery Unit, , Hadassah Hebrew University Medical Center, ; Jerusalem, Israel
                [11 ]ISNI 0000 0000 9950 8111, GRID grid.413731.3, Department of General Surgery, , Rambam Health Care Campus, ; Haifa, Israel
                [12 ]ISNI 0000 0004 0449 3295, GRID grid.415402.6, Trauma and Acute Care Surgery, , Scripps Memorial Hospital La Jolla, ; La Jolla, CA USA
                [13 ]ISNI 0000 0004 0367 5222, GRID grid.475010.7, Pathology and Laboratory Medicine, VA Boston Healthcare System, , West Roxbury MA and BU School of Medicine, ; Boston, MA USA
                [14 ]Department of Internal Medicine, University Hospital, Dr. José E. González, Monterrey, Mexico
                [15 ]ISNI 0000000109410645, GRID grid.11794.3a, Department of Surgery, , University of Santiago de Compostela, ; A Coruña, Spain
                [16 ]GRID grid.439210.d, Department of General Surgery, , Medway Maritime Hospital, ; Gillingham, Kent UK
                [17 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Surgery, Division of Acute Care Surgery, , University of Michigan, ; Ann Arbor, MI USA
                [18 ]ISNI 0000 0001 2156 6140, GRID grid.268154.c, Department of Surgery, , West Virginia University Charleston Division, ; Charleston, WV USA
                [19 ]ISNI 0000 0001 2159 8361, GRID grid.5120.6, Faculty of Medicine, , Transilvania University, Infectious Diseases Hospital, ; Brasov, Romania
                [20 ]ISNI 0000 0000 9852 649X, GRID grid.43582.38, Riverside University Health System Medical Center and Loma Linda University School of Medicine, ; Moreno Valley, CA USA
                [21 ]Emergency Surgery Unit, San Filippo Neri’s Hospital, Rome, Italy
                [22 ]Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
                [23 ]ISNI 0000 0001 2162 9631, GRID grid.5522.0, Department of Infectious Diseases, , Jagiellonian University, Medical College, ; Kraków, Poland
                [24 ]ISNI 0000 0004 0428 8304, GRID grid.412274.6, Department of Surgery, , Tbilisi State Medical University, Kipshidze Central University Hospital, ; Tbilisi, Georgia
                [25 ]ISNI 0000 0004 1757 1969, GRID grid.8158.4, Department of Surgical Sciences, , Cannizzaro Hospital, University of Catania, ; Catania, Italy
                [26 ]ISNI 0000 0004 0622 5016, GRID grid.120073.7, Department of Surgery, , Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, ; Cambridge, UK
                [27 ]ISNI 0000 0001 1089 1079, GRID grid.412430.0, Clinical Infectious Diseases Hospital, Ovidius University, ; Constanta, Romania
                [28 ]Department of General, Visceral and Thoracic Surgery, Klinikum Peine, Hospital of Medical University Hannover, Peine, Germany
                [29 ]Vital Care, Inc, Meridian, MS USA
                [30 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Surgery, , Stanford University, ; Stanford, CA USA
                [31 ]ISNI 0000 0001 0723 2494, GRID grid.411087.b, Division of Trauma Surgery, Hospital de Clinicas, School of Medical Sciences, , University of Campinas, ; Campinas, Brazil
                [32 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, Service of Gastroenterology and Hepatology, , Geneva University Hospital, ; Genève, Switzerland
                [33 ]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Department of Surgery, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
                [34 ]ISNI 0000 0001 2188 8502, GRID grid.266832.b, University of New Mexico School of Medicine, ; Albuquerque, NM USA
                [35 ]ISNI 0000 0001 2176 8535, GRID grid.8073.c, Critical Care Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, , Universidade da Coruña (UDC), ; A Coruña, Spain
                [36 ]ISNI 0000000103426662, GRID grid.10251.37, Department of Surgery Mansoura, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
                [37 ]ISNI 0000 0001 2170 9332, GRID grid.411198.4, Surgery Department, Hospital Universitario (HU) Terezinha de Jesus da Faculdade de Ciencias Medicas e da Saude de Juiz de Fora (SUPREMA), , Hospital Universitario (HU) Universidade Federal de Juiz de Fora (UFJF), ; Juiz de Fora, Brazil
                [38 ]ISNI 0000 0001 2177 007X, GRID grid.415490.d, Department of Surgery, , Queen Elizabeth Hospital, ; Birmingham, UK
                [39 ]Unit of Endocrine, Head, and Neck Surgery and Unit of Surgical Infections Support, Department of General Surgery, Parc Taulí, Hospital Universitari, Sabadell, Spain
                [40 ]GRID grid.415667.7, Department of Medicine, , Milton Keynes University Hospital NHS Foundation Trust, ; Milton Keynes, Buckinghamshire UK
                [41 ]GRID grid.416438.c, Department of Surgery, , St. Josef Hospital, Ruhr University Bochum, ; Bochum, Germany
                [42 ]ISNI 0000 0004 0371 8173, GRID grid.411633.2, Department of Surgery, , Ilsan Paik Hospital, Inje University College of Medicine, ; Goyang, Republic of Korea
                [43 ]ISNI 0000 0001 2177 007X, GRID grid.415490.d, Department of Gastroenterology, , Queen Elizabeth Hospital, ; Birmingham, UK
                [44 ]ISNI 0000 0004 0455 1723, GRID grid.411487.f, General Surgery Department, , Magee Womens Hospital, UPMC, ; Pittsburgh, USA
                [45 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Surgery, VA Boston Health Care System, , Boston University and Harvard Medical School, ; Boston, MA USA
                [46 ]Global Alliance for Infections in Surgery, Porto, Portugal
                [47 ]ISNI 0000 0001 2294 3534, GRID grid.11875.3a, School of Medical Sciences, , University Sains Malaysia, ; Kota Bharu, Kelantan Malaysia
                [48 ]ISNI 0000 0000 8660 3507, GRID grid.419579.7, Department of Pharmacy Practice, , St Louis College of Pharmacy, ; St Louis, MO USA
                [49 ]Faculty of Mediine University of Belgrade Clinic for Surgery “Nikola Spasic”, University Clinical Center “Zvezdara” Belgrade, Belgrade, Serbia
                [50 ]ISNI 0000000121791997, GRID grid.251993.5, Department of Surgery, Jacobi Medical Center, , Albert Einstein College of Medicine, ; Bronx, NY USA
                [51 ]ISNI 0000 0000 9950 5666, GRID grid.15485.3d, Abdominal Center, , Helsinki University Hospital Meilahti, ; Helsinki, Finland
                [52 ]ISNI 0000 0004 1937 0490, GRID grid.10223.32, Department of Surgery, Faculty of Medicine Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand
                [53 ]ISNI 0000 0001 2289 5077, GRID grid.412213.7, Department of Surgery, , Universidad Nacional de Asuncion, ; Asuncion, Paraguay
                [54 ]ISNI 0000 0004 1771 1642, GRID grid.412572.7, Department of Surgery, , Post-Graduate Institute of Medical Sciences, ; Rohtak, India
                [55 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Surgery, , Washington University School of Medicine, ; Saint Louis, USA
                [56 ]ISNI 0000 0001 2342 7339, GRID grid.14442.37, Department of Infectious Diseases and Clinical Microbiology, , Hacettepe University Faculty of Medicine, ; Ankara, Turkey
                [57 ]Department of Surgery, University of Colorado, Denver Health Medical Center, Denver, CO USA
                [58 ]ISNI 0000 0004 1936 8091, GRID grid.15276.37, Department of Surgery, , University of Florida, ; Gainesville, FL USA
                [59 ]ISNI 0000 0001 2295 7397, GRID grid.8271.c, Department of Surgery, Fundación Valle del Lili, Hospital Universitario del Valle, , Universidad del Valle, ; Cali, Colombia
                [60 ]Infectious Diseases Unit, Bolzano Central Hospital, Bolzano, Italy
                [61 ]National Institute for Infectious Diseases - INMI - Lazzaro Spallanzani IRCCS, Rome, Italy
                [62 ]ISNI 0000000106861985, GRID grid.28911.33, Gastroenterology Department, , Centro Hospitalar e Universitário de Coimbra, ; Coimbra, Portugal
                [63 ]Department of Surgery, Anadolu Medical Center, Kocaali, Turkey
                [64 ]Department of Abdominal and General Surgery, General Hospital Jesenice, Jesenice, Slovenia
                [65 ]ISNI 0000 0001 0726 0380, GRID grid.35371.33, Department of Surgery, , Medical University of Plovdiv, ; Plovdiv, Bulgaria
                [66 ]GRID grid.414603.4, Division of Emergency Surgery, Department of Surgery, , Fondazione Policlinico Universitario A. Gemelli IRCCS, ; Rome, Italy
                [67 ]GRID grid.240988.f, Department of Surgery, , Tan Tock Seng Hospital, ; Singapore, Singapore
                [68 ]ISNI 0000 0000 9120 6856, GRID grid.416651.1, Department of Infectious Diseases, , Istituto Superiore di Sanità, ; Rome, Italy
                [69 ]GRID grid.414271.5, Infectious Diseases and Intensive Care Unit, , Pontchaillou University Hospital, ; Rennes, France
                [70 ]ISNI 0000 0001 2194 0956, GRID grid.10267.32, First Department of Surgery, Faculty of Medicine, , Masaryk University Brno and University Hospital of St. Ann Brno, ; Brno, Czech Republic
                [71 ]ISNI 0000 0000 9100 9940, GRID grid.411798.2, First Department of Surgery, First Faculty of Medicine, , Charles University in Prague and General University Hospital in Prague, ; Prague, Czech Republic
                [72 ]GRID grid.412311.4, Clinic of Infectious Diseases, , St Orsola-Malpighi University Hospital, ; Bologna, Italy
                [73 ]ISNI 0000000417571846, GRID grid.7637.5, Department of Clinical and Experimental Sciences, , University of Brescia, ; Brescia, Italy
                [74 ]GRID grid.411482.a, Emergency Surgery Department, , Maggiore Parma Hospital, ; Parma, Italy
                Article
                228
                10.1186/s13017-019-0228-3
                6394026
                30858872
                21f4ead7-ef53-4243-a4a0-a49143174311
                © The Author(s). 2019

                Open AccessThis 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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 January 2019
                : 17 February 2019
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Surgery
                clostridioides difficile infection,clostridium difficile infection,pseudomembranous colitis,antimicrobial treatment,fecal microbiota transplantation,infection control,antimicrobial stewardship

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