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Clostridium Difficile Toxin

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https://www.readbyqxmd.com/read/28213939/protective-antibodies-against-clostridium-difficile-are-present-in-intravenous-immunoglobulin-and-are-retained-in-humans-following-its-administration
#1
Ola H Negm, Brendon MacKenzie, Mohamed R Hamed, Omar Aj Ahmad, Clifford C Shone, David P Humphreys, K Ravi Acharya, Christine E Loscher, Izabela Marszalowska, Mark Lynch, Mark H Wilcox, Tanya M Monaghan
The prevalence of serum antibodies against C. difficile (CD) toxins A and B in healthy populations have prompted interest in evaluating the therapeutic activity of intravenous immunoglobulin (IVIg) in individuals experiencing severe or recurrent C. difficile infection (CDI). Despite some promising case reports, a definitive clinical role for IVIg in CDI remains unclear. Contradictory results may be attributed to a lack of consensus regarding optimal dose, timing of administration and patient selection as well as variability in specific antibody content between commercial preparations...
February 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28198085/the-alternative-sigma-factor-%C3%AF-b-plays-a-crucial-role-in-adaptive-strategies-of-clostridium-difficile-during-gut-infection
#2
Nicolas Kint, Claire Janoir, Marc Monot, Sandra Hoys, Olga Soutourina, Bruno Dupuy, Isabelle Martin-Verstraete
Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification, and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σ(B) . In this work, we studied the role of σ(B) in the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σ(B) controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis, and the management of stresses...
February 15, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28192156/evaluation-of-two-novel-chemiluminescence-immunoassays-for-the-detection-of-clostridium-difficile-glutamate-dehydrogenase-and-toxin-a-b
#3
Annette Blaich, Reno Frei, Carine Castellano, Christine Kiessling, Angelika Geschke, Katharina M Rentsch, Adrian Egli
A novel immunoassay for Clostridium difficile glutamate dehydrogenase (GDH) and toxin A&B (LIAISON, DiaSorin) was compared to another GDH assay (Alere), PCR and toxigenic culture. The GDH-DiaSorin is slightly more sensitive than the GDH-Alere. Sensitivity of the Toxin-Diasorin test is in accordance to the sensitivity of other immunoassays in literature.
February 10, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28182338/evaluation-of-nested-polymerase-chain-reaction-and-immunoassay-for-rapid-diagnosis-of-clostridium-difficile-in-children-with-community-acquired-diarrhea
#4
Ahmed Elewa, Maysaa El Sayed-Zaki
BACKGROUND: Clostridium difficile (C. difficile) is a known pathogen associated with diarrhea especially in hospital acquired diarrhea. Yet, it is being recognized as a probable etiology for community acquired diarrhea. The aim of the present study was to detect the presence of C. difficile as a pathogen causing community acquired diarrhea in children and to verify the value of different laboratory methods for diagnosis, namely specific culture, immunoassay for toxin detection, and nested polymerase chain reaction (nested-PCR)...
February 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28181098/effect-of-aging-on-the-composition-of-fecal-microbiota-in-donors-for-fmt-and-its-impact-on-clinical-outcomes
#5
Rohit Anand, Yang Song, Shashank Garg, Mohit Girotra, Amitasha Sinha, Anita Sivaraman, Laila Phillips, Sudhir K Dutta
BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as an effective therapy for the treatment of recurrent Clostridium difficile infection (RCDI). Selecting an appropriate donor is vital to the success of FMT. However, the relationship between age of donors and the efficacy of FMT has not been examined to date. The aim of this study was to examine the effect of age of healthy donors on their fecal microbiota and assess the impact of these changes on the clinical efficacy of FMT...
February 8, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28181032/comprehensive-evaluation-of-chemiluminescent-immunoassays-for-the-laboratory-diagnosis-of-clostridium-difficile-infection
#6
A Makristathis, I Zeller, D Mitteregger, M Kundi, A M Hirschl
For the microbiological diagnosis of a Clostridium (C.) difficile infection (CDI), a two-test algorithm consisting of a C. difficile glutamate dehydrogenase (GDH)-immunoassay followed by a toxin-immunoassay in positive cases is widely used. In this study, two chemiluminescent immunoassays (CLIAs), one for GDH and the other for the toxins A and B, have been evaluated systematically using appropriate reference methods. Three-hundred diarrhoeal stool specimens submitted for CDI diagnosis were analysed by the LIAISON CLIAs (DiaSorin)...
February 8, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28177534/laboratory-diagnosis-of-clostridium-difficile-infection-comparison-of-techlab-c-diff-quik-chek-complete-xpert-c-difficile-and-multistep-algorithmic-approach
#7
Ja Young Seo, Ji Hun Jeong, Kyung Hee Kim, Jeong-Yeal Ahn, Pil-Whan Park, Yiel-Hea Seo
BACKGROUND: Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. METHODS: Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C...
February 8, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28173695/the-american-cockroach-peptide-periplanetasin-2-blocks-clostridium-difficile-toxin-a-induced-cell-damage-and-inflammation-in-the-gut
#8
Ji Hong, Peng Zhang, I Na Yoon, Jae Sam Hwang, Jin Ku Kang, Ho Kim
Clostridium difficile, which causes pseudomembranous colitis, releases toxin A and toxin B. These toxins are considered to be the main causative agents for the disease pathogenesis, and their expression is associated with a marked increase of apoptosis in mucosal epithelial cells. Colonic epithelial cells are believed to form a physical barrier between the lumen and the submucosa, and abnormally increased mucosal epithelial cell apoptosis is considered to be an initial step in gut inflammation responses. Therefore, one approach to treating pseudomembranous colitis would be to develop agents that block the mucosal epithelial cell apoptosis caused by toxin A, thus restoring barrier function and curing inflammatory responses in the gut...
February 7, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28167669/mucosal-antibodies-to-the-c-terminus-of-toxin-a-prevent-colonization-of-clostridium-difficile
#9
Huynh A Hong, Krisztina Hitri, Siamand Hosseini, Natalia Kotowicz, Donna Bryan, Fatme Mawas, Anthony J Wilkinson, Annie van Broekhoven, Jonathan Kearsey, Simon M Cutting
Mucosal immunity is considered important for protection to Clostridium difficile infection (CDI). We show that in hamsters immunized with Bacillus subtilis spores expressing a carboxy-terminal segment (TcdA26-39) of C. difficile toxin A no colonization occurs in protected animals when challenged with C. difficile strain 630. By contrast, animals immunized with toxoids showed no protection and remained fully colonized. As well as neutralizing toxins, antibodies to TcdA26-39 (but not to toxoids), whether raised to the recombinant protein, or to TcdA26-39 expressed on the B...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28166328/comparative-effectiveness-of-vancomycin-and-metronidazole-for-the-prevention-of-recurrence-and-death-in-patients-with-clostridium-difficile-infection
#10
Vanessa W Stevens, Richard E Nelson, Elyse M Schwab-Daugherty, Karim Khader, Makoto M Jones, Kevin A Brown, Tom Greene, Lindsay D Croft, Melinda Neuhauser, Peter Glassman, Matthew Bidwell Goetz, Matthew H Samore, Michael A Rubin
Importance: Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. Objective: To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI...
February 6, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28164522/detection-of-clostridium-difficile-in-fecal-specimens-a-comparative-evaluation-of-nucleic-acid-amplification-test-and-toxigenic-culture
#11
Shima Lotfian, Masoumeh Douraghi, Amir Aliramezani, Sedighe Ghourchian, Abdolfatah Sarrafnejad, Hojjat Zeraati
BACKGROUND: The available data regarding Clostridium difficile infections (CDIs) in developing countries are scarce. This may be related in part to the complexity of anaerobic bacterial culture and/or cytotoxicity assays of C. difficile. Here, we evaluated the diagnostic efficacy of PCR in comparison with toxigenic culture for direct detection of conserved genes as well as toxin genes of C. difficile in fecal specimens of patients with clinical symptoms of CDI. METHODS: Loose or soft feces from 171 patients suspected of having C...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28158441/contribution-to-clostridium-difficile-transmission-of-symptomatic-patients-with-toxigenic-strains-who-are-fecal-toxin-negative
#12
Damian Pc Mawer, David W Eyre, David Griffiths, Warren N Fawley, Jessica Sh Martin, T Phuong Quan, Timothy Ea Peto, Derrick W Crook, A Sarah Walker, Mark H Wilcox
No abstract text is available yet for this article.
February 3, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28153559/clinical-and-laboratory-features-of-the-most-common-clostridium-difficile-ribotypes-isolated-in-belgium
#13
F Neely, M-L Lambert, J Van Broeck, M Delmée
BACKGROUND: Previous studies comparing Clostridium difficile infection (CDI) due to different ribotypes have been conflicting, and many have only compared small numbers of cases or few ribotypes. AIM: To compare patient and episode characteristics for CDI due to different ribotypes. METHODS: The ribotyping results from 3333 toxin-producing isolates collected from 110 Belgian hospitals between October 2010 and December 2015 were matched to clinical data from the national CDI surveillance database...
December 18, 2016: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28145453/high-prevalence-of-toxigenic-clostridium-difficile-in-public-space-lawns-in-western-australia
#14
Peter Moono, Su Chen Lim, Thomas V Riley
Clostridium difficile is a well-established hospital pathogen. Recently, it has been detected increasingly in patients without hospital contact. Given this rise in community associated infections with C. difficile, we hypothesized that the environment could play an important role in transmission of spores outside the hospital. Lawn samples (311) collected in public spaces in the metropolitan area of Perth, Western Australia, from February to June 2016 were cultured for C. difficile. C. difficile was isolated from the samples by direct and enrichment culture, and characterized by standard molecular methods using toxin gene PCR and ribotyping...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28125650/development-of-a-novel-vaccine-containing-binary-toxin-for-the-prevention-of-clostridium-difficile-disease-with-enhanced-efficacy-against-nap1-strains
#15
Susan Secore, Su Wang, Julie Doughtry, Jinfu Xie, Matt Miezeiewski, Richard R Rustandi, Melanie Horton, Rachel Xoconostle, Bei Wang, Catherine Lancaster, Adam Kristopeit, Sheng-Ching Wang, Sianny Christanti, Salvatore Vitelli, Marie-Pierre Gentile, Aaron Goerke, Julie Skinner, Erica Strable, David S Thiriot, Jean-Luc Bodmer, Jon H Heinrichs
Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality...
2017: PloS One
https://www.readbyqxmd.com/read/28122873/rising-stakes-for-healthcare-associated-infection-prevention-implications-for-the-clinical-microbiology-laboratory-revised
#16
Daniel J Diekema
Healthcare associated infection (HAI) rates are subject to public reporting, and are linked to hospital reimbursement from the Centers for Medicare and Medicaid Services (CMS). The increasing pressure to lower HAI rates comes at a time when advances in the clinical microbiology laboratory (CML) provide more precise and sensitive tests, altering HAI detection in ways that may increase reported HAI rates. I review how changing CML practices can impact HAI rates, and how the financial implications of HAI metrics may produce pressure to change diagnostic testing practices...
January 25, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28121498/bezlotoxumab-for-prevention-of-recurrent-clostridium-difficile-infection
#17
RANDOMIZED CONTROLLED TRIAL
Mark H Wilcox, Dale N Gerding, Ian R Poxton, Ciaran Kelly, Richard Nathan, Thomas Birch, Oliver A Cornely, Galia Rahav, Emilio Bouza, Christine Lee, Grant Jenkin, Werner Jensen, You-Sun Kim, Junichi Yoshida, Lori Gabryelski, Alison Pedley, Karen Eves, Robert Tipping, Dalya Guris, Nicholas Kartsonis, Mary-Beth Dorr
Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. Methods We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis...
26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28120176/fidaxomicin-for-treatment-of-clostridium-difficile-infection-in-clinical-practice-a-prospective-cohort-study-in-a-french-university-hospital
#18
Marie Pichenot, Rozenn Héquette-Ruz, Remi Le Guern, Bruno Grandbastien, Clément Charlet, Frédéric Wallet, Sophie Schiettecatte, Fanny Loeuillet, Benoit Guery, Tatiana Galperine
PURPOSE: Two randomized controlled trials (RCTs) showed the non-inferiority of fidaxomicin compared with vancomycin for Clostridium difficile infection (CDI) treatment and its superiority regarding recurrence rate. The aim of this study was to evaluate fidaxomicin's efficacy in clinical practice. METHODS: This single-center prospective cohort study included hospitalized patients treated with fidaxomicin for CDI. Demographic, clinical and biological data were collected...
January 24, 2017: Infection
https://www.readbyqxmd.com/read/28119780/prevalence-and-molecular-epidemiology-of-clostridium-difficile-infection-in-thailand
#19
P Putsathit, M Maneerattanaporn, P Piewngam, P Kiratisin, T V Riley
Little is known about Clostridium difficile infection (CDI) in Asia generally, and specifically in Thailand. Given the high prevalence of inappropriate antibiotic usage in this region, CDI is likely to be common. This study investigated the prevalence and molecular epidemiology of CDI in Thailand. Stool specimens collected from inpatients with diarrhoea at Siriraj hospital in Bangkok (n = 422) were cultured on ChromID Cdiff agar and any presumptive C. difficile colonies were identified, PCR ribotyped and toxin profiled...
January 2017: New Microbes and New Infections
https://www.readbyqxmd.com/read/28119311/salubrinal-protects-against-clostridium-difficile-toxin-b-induced-ct26-cell-death
#20
Shuyi Chen, Chunli Sun, Huawei Gu, Haiying Wang, Shan Li, Yi Ma, Jufang Wang
Clostridium difficile(C. difficile) is considered to be the major cause of the antibiotic-associated diarrhea and pseudomembranous colitis in animals and humans. The prevalence of C. difficile infections (CDI) has been increasing since 2000. Two exotoxins of C. difficile, Toxin A (TcdA) and Toxin B (TcdB), are the main virulence factors of CDI, which can induce glucosylation of Rho GTPases in host cytosol, leading to cell morphological changes, cell apoptosis, and cell death. The mechanism of TcdB-induced cell death has been investigated for decades, but it is still not completely understood...
January 23, 2017: Acta Biochimica et Biophysica Sinica
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