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Clostridium Difficile Toxin

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https://www.readbyqxmd.com/read/28930913/the-effect-of-lactoferrin-and-pepsin-treated-lactoferrin-on-iec-6-cell-damage-induced-by-clostridium-difficile-toxin-b
#1
Kosuke Otake, Norio Sato, Ayako Kitaguchi, Takayuki Irahara, Satoru Murata, Keiichiro Shiraga, Yuichi Ogawa, Takahiro K Fujiwara, Kaoru Koike, Hiroyuki Yokota
Clostridium difficile infections (CDI) have recently increased worldwide. Some CDI progress to fulminant and recurrent CDI and are associated with high mortality and morbidity. CD produces toxins A and B, which cause intestinal mucosal damage, although toxin B exhibits greater cytotoxicity. Pepsin-treated lactoferrin (PLF) is the decomposed product of lactoferrin (LF), a multifunctional glycoprotein with anti-inflammatory properties. Here, we investigate the effects of LF and PLF in toxin B-stimulated rat intestinal epithelial (IEC-6) cells...
September 19, 2017: Shock
https://www.readbyqxmd.com/read/28929960/-antimicrobial-susceptibilities-and-molecular-characterization-of-toxin-positive-clostridium-difficile-isolates-the-first-report-on-the-presence-of-hypervirulent-strains-from-turkey
#2
Emrah Salman, Belkıs Levent, Zeynep Ceren Karahan
Clostridium difficile infection is one of the most important hospital-acquired infections. Infections caused by hypervirulent C.difficile strains which produce toxins at high levels, have higher morbidity and mortality rates, more complications and relapses. They are characterized by higher sporulation ratios and resistance rates for fluoroquinolones. In order to prevent serious morbidities, mortalities and remarkable increase in health costs, highly pathogenic C.difficile strains must be identified before causing severe outbreaks...
July 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28919674/prevalence-of-enteropathogens-and-their-antibiotic-sensitivity-pattern-in-puppies-with-hemorrhagic-gastroenteritis
#3
A Kokila Priya, M Balagangatharathilagar, D Chandrasekaran, M Parthiban, S Prathaban
AIM: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. MATERIALS AND METHODS: The canine HGE activity index, with little modification, was adopted to identify Grade III/severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control...
August 2017: Veterinary World
https://www.readbyqxmd.com/read/28902923/molecular-microbiological-and-clinical-characterization-of-clostridium-difficile-isolates-from-tertiary-care-hospitals-in-colombia
#4
Clara Lina Salazar, Catalina Reyes, Santiago Atehortua, Patricia Sierra, Margarita María Correa, Daniel Paredes-Sabja, Emma Best, Warren N Fawley, Mark Wilcox, Ángel González
In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed...
2017: PloS One
https://www.readbyqxmd.com/read/28899610/nosocomial-acquired-and-community-onset-clostridium-difficile-infection-at-an-academic-hospital-in-italy-epidemiology-recurrences-and-toxin-genes-distribution
#5
Valeria Visconti, Grazia Brunetti, Maria Rosaria Cuomo, Alessandra Giordano, Giammarco Raponi
Toxinogenic Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea. In this retrospective cohort study the molecular epidemiology of hospital-acquired and community-associated CDI was investigated in patients admitted to a tertiary care hospital. CD in stools samples was revealed by a two steps diagnostic algorithm, firstly screening for positivity to GDH antigen and thereafter RT-PCR analysis. Increased CDI incidence was observed ranging from 1.70episodes/10000patient-days in the 1st year, to 2...
September 9, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28893366/fidaxomicin-reduces-early-toxin-a-and-b-production-and-sporulation-in-clostridium-difficilein-vitro
#6
Michael J Aldape, Aaron E Packham, Dustin D Heeney, Savannah N Rice, Amy E Bryant, Dennis L Stevens
PURPOSE: Fidaxomicin, a macrocyclic antibiotic, has been approved for the treatment of Clostridium difficile infection (CDI). Previous work by our group has demonstrated that some antibiotics at sub-inhibitory concentrations stimulate early toxin production and sporulation by C. difficile. Prior studies revealed that fidaxomicin, when added to late stationary-phase organisms, reduced exotoxin production and spore formation by C. difficile. However, the ability of fidaxomicin to trigger early virulence factor production and spore formation has never been investigated...
September 12, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28891459/prevalence-of-clostridium-difficile-infection-and-colonization-in-a-tertiary-hospital-and-elderly-community-of-north-eastern-peninsular-malaysia
#7
N H Zainul, Z F Ma, A Besari, H Siti Asma, R A Rahman, D A Collins, N Hamid, T V Riley, Y Y Lee
Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C...
September 11, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28878013/new-class-of-precision-antimicrobials-redefines-role-of-clostridium-difficile-s-layer-in-virulence-and-viability
#8
Joseph A Kirk, Dana Gebhart, Anthony M Buckley, Stephen Lok, Dean Scholl, Gillian R Douce, Gregory R Govoni, Robert P Fagan
There is a medical need for antibacterial agents that do not damage the resident gut microbiota or promote the spread of antibiotic resistance. We recently described a prototypic precision bactericidal agent, Av-CD291.2, which selectively kills specific Clostridium difficile strains and prevents them from colonizing mice. We have since selected two Av-CD291.2-resistant mutants that have a surface (S)-layer-null phenotype due to distinct point mutations in the slpA gene. Using newly identified bacteriophage receptor binding proteins for targeting, we constructed a panel of Avidocin-CDs that kills diverse C...
September 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28874882/glucosyltransferase-activity-of-clostridium-difficile-toxin-b-triggers-autophagy-mediated-cell-growth-arrest
#9
Ruina He, Jingyu Peng, Pengfei Yuan, Junjiao Yang, Xiaoji Wu, Yinan Wang, Wensheng Wei
Autophagy is a bulk cell-degradation process that occurs through the lysosomal machinery, and many reports have shown that it participates in microbial pathogenicity. However, the role of autophagy in Clostridium difficile infection (CDI), the leading cause of antibiotics-associated diarrhea, pseudomembranous colitis and even death in severe cases, is not clear. Here we report that the major virulent factor toxin B (TcdB) of Clostridium difficile elicits a strong autophagy response in host cells through its glucosyltransferase activity...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874406/revisiting-the-role-of-csp-family-proteins-in-regulating-clostridium-difficile-spore-germination
#10
Yuzo Kevorkian, Aimee Shen
Clostridium difficile causes considerable healthcare-associated gastrointestinal disease that is transmitted by its metabolically dormant spore form. Upon entering the gut, C. difficile spores germinate and outgrow to produce vegetative cells that release disease-causing toxins. C. difficile spore germination depends on the Csp family of (pseudo)proteases and the cortex hydrolase, SleC. The CspC pseudoprotease functions as a bile salt germinant receptor that activates the protease CspB, which in turn proteolytically activates SleC zymogen...
September 5, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28865041/bezlotoxumab-a-review-in-preventing-clostridium-difficile-infection-recurrence
#11
Emma D Deeks
Bezlotoxumab (Zinplava™) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk. It is the first agent approved for recurrence prevention and is administered as a single intravenous infusion in conjunction with standard-of-care (SoC) antibacterial treatment for CDI. In well-designed, placebo-controlled, phase 3 trials (MODIFY 1 and 2), a single infusion of bezlotoxumab, given in combination with SoC antibacterial therapy for CDI in adults, was effective in reducing CDI recurrence in the 12 weeks post-treatment, with this benefit being seen mainly in the patients at high recurrence risk...
September 1, 2017: Drugs
https://www.readbyqxmd.com/read/28851988/nosocomial-transmission-of-clostridium-difficile-genotype-st81-in-a-general-teaching-hospital-in-china-traced-by-whole-genome-sequencing
#12
Juanxiu Qin, Yingxin Dai, Xiaowei Ma, Yanan Wang, Qianqian Gao, Huiying Lu, Tianming Li, Hongwei Meng, Qian Liu, Min Li
Clostridium difficile infection (CDI) is increasingly recognized globally as a cause of significant morbidity and mortality. This study aimed to provide insight into the various dynamics of C. difficile transmission and infection in the hospital. We monitored the toxin and resistance profiles as well as evolutionary relationships of C. difficile strains to determine the epidemiology over time in a teaching hospital in Shanghai, China between May 2014 and August 2015. The CDI incidence of inpatients and outpatients were 67...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842504/functional-defects-in-clostridium-difficile-tcdb-toxin-uptake-identify-cspg4-receptor-binding-determinants
#13
Pulkit Gupta, Zhifen Zhang, Seiji N Sugiman-Marangos, John Tam, Swetha Raman, Jean-Philippe Julien, Heather K Kroh, D Borden Lacy, Nicholas Murgolo, Kavitha Bekkari, Alex G Therien, Lorraine D Hernandez, Roman A Melnyk
Clostridium difficile is a major nosocomial pathogen that produces two exotoxins, TcdA and TcdB, with TcdB thought to be the primary determinant in human disease. TcdA and TcdB are large, multi-domain proteins, each harboring a cytotoxic glucosyltransferase domain that is delivered into the cytosol from endosomes via a translocation domain following receptor-mediated endocytosis of toxins from the cell surface. While there are currently no known host cell receptors for TcdA, three cell-surface receptors for TcdB have been identified: CSPG4, NECTIN3 and FZD1/2/7...
August 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28837182/bezlotoxumab-for-the-treatment-of-clostridium-difficile-associated-diarrhea
#14
R Thakare, A Dasgupta, S Chopra
Diarrhea caused by Clostridium difficile is one of the major emerging threats to modern healthcare systems worldwide. Although C. difficile spores are present in the gut innocuously, because of repeated broad-spectrum antibiotic therapy, the spores germinate with concomitant release of exotoxin A and B, resulting in mild to severe diarrhea. Antibiotic therapy is augmented by addition of the humanized antibodies actoxumab and bezlotoxumab to prevent the action of exotoxins A and B, respectively, since they provide passive immunity...
July 2017: Drugs of Today
https://www.readbyqxmd.com/read/28830806/an-outbreak-of-clostridium-difficile-infections-due-to-a-new-pcr-ribotype-826-epidemiological-and-microbiological-analyses
#15
Monique J T Crobach, Anne F Voor In 't Holt, Cornelis W Knetsch, Sofie M van Dorp, Willeke Bras, Celine Harmanus, Ed J Kuijper, Margreet C Vos
OBJECTIVES: The aim was to investigate an unusual outbreak of 5 patients with in total 8 episodes of a Clostridium difficile infection (CDI) on a gastro intestinal surgical ward of a Dutch tertiary care university affiliated hospital. METHODS: Clinical case investigations and laboratory analyses were performed. Laboratory analyses included PCR ribotyping, MLVA typing, toxinotyping, antimicrobial susceptibility testing and whole genome sequencing. RESULTS: The outbreak was associated with recurrent and severe disease in 2 out of 5 patients...
August 19, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28816966/causes-of-hematochezia-and-hemorrhagic-antibiotic-associated-colitis-in-children-and-adolescents
#16
Laura Stampfer, Andrea Deutschmann, Elisabeth Dür, Franz G Eitelberger, Theresia Fürpass, Gregor Gorkiewicz, Peter Heinz-Erian, Ingrid Heller, Kathrin Herzog, Barbara Hopfer, Reinhold Kerbl, Evelyn Klug, Robert Krause, Eva Leitner, Christoph Mache, Thomas Müller, Jasmin Pansy, Mirjam Pocivalnik, Eva Scheuba, Georg Schneditz, Gerolf Schweintzger, Edith Sterniczky, Ellen Zechner, Almuthe C Hauer, Christoph Högenauer, Karl Martin Hoffmann
Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children. We further investigated the relevance of antibiotic-associated hemorrhagic colitis in children, especially if caused by Klebsiella oxytoca.Infants, children, and adolescents with hematochezia were recruited prospectively. Patients were grouped according to age (<1 year, 1-5 years, 6-13 years, >14 years)...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28814976/analysis-of-proteomes-released-from-in-vitro-cultured-eight-clostridium-difficile-pcr-ribotypes-revealed-specific-expression-in-pcr-ribotypes-027-and-176-confirming-their-genetic-relatedness-and-clinical-importance-at-the-proteomic-level
#17
Jiri Dresler, Marcela Krutova, Alena Fucikova, Jana Klimentova, Veronika Hruzova, Miloslava Duracova, Katerina Houdkova, Barbora Salovska, Jana Matejkova, Martin Hubalek, Petr Pajer, Libor Pisa, Otakar Nyc
BACKGROUND: Clostridium difficile is the causative agent of C. difficile infection (CDI) that could be manifested by diarrhea, pseudomembranous colitis or life-threatening toxic megacolon. The spread of certain strains represents a significant economic burden for health-care. The epidemic successful strains are also associated with severe clinical features of CDI. Therefore, a proteomic study has been conducted that comprises proteomes released from in vitro cultured panel of eight different PCR ribotypes (RTs) and employs the combination of shotgun proteomics and label-free quantification (LFQ) approach...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28813492/point-prevalence-survey-of-healthcare-facility-onset-healthcare-associated-clostridium-difficile-infection-in-greek-hospitals-outside-the-intensive-care-unit-the-c-define-study
#18
Athanasios Skoutelis, Angelos Pefanis, Sotirios Tsiodras, Nikolaos V Sipsas, Moyssis Lelekis, Marios C Lazanas, Panagiotis Gargalianos, George N Dalekos, Emmanuel Roilides, George Samonis, Efstratios Maltezos, Dimitrios Hatzigeorgiou, Malvina Lada, Symeon Metallidis, Athena Stoupis, Georgios Chrysos, Lazaros Karnesis, Styliani Symbardi, Chariclia V Loupa, Helen Giamarellou, Ioannis Kioumis, Helen Sambatakou, Epameinondas Tsianos, Maria Kotsopoulou, Areti Georgopali, Klairi Liakou, Stavroula Perlorentzou, Stamatina Levidiotou, Marina Giotsa-Toutouza, Helen Tsorlini-Christoforidou, Ilias Karaiskos, Georgia Kouppari, Eleftheria Trikka-Graphakos, Maria-Anna Ntrivala, Kate Themeli-Digalaki, Anastasia Pangalis, Melina Kachrimanidou, Maria Martsoukou, Stergios Karapsias, Maria Panopoulou, Sofia Maraki, Anagnostina Orfanou, Efthymia Petinaki, Maria Orfanidou, Vasiliki Baka, Antonios Stylianakis, Iris Spiliopoulou, Stavroula Smilakou, Loukia Zerva, Evangelos Vogiatzakis, Eleni Belesiotou, Charalambos A Gogos
BACKGROUND: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI...
2017: PloS One
https://www.readbyqxmd.com/read/28813461/epidemiology-of-clostridium-difficile-in-infants-in-oxfordshire-uk-risk-factors-for-colonization-and-carriage-and-genetic-overlap-with-regional-c-difficile-infection-strains
#19
Nicole Stoesser, David W Eyre, T Phuong Quan, Heather Godwin, Gemma Pill, Emily Mbuvi, Alison Vaughan, David Griffiths, Jessica Martin, Warren Fawley, Kate E Dingle, Sarah Oakley, Kazimierz Wanelik, John M Finney, Melina Kachrimanidou, Catrin E Moore, Sherwood Gorbach, Thomas V Riley, Derrick W Crook, Tim E A Peto, Mark H Wilcox, A Sarah Walker
BACKGROUND: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. METHODS: Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C...
2017: PloS One
https://www.readbyqxmd.com/read/28811244/comparison-of-the-clinical-course-of-clostridium-difficile-infection-in-gdh-positive-toxin-negative-patients-diagnosed-by-pcr-to-those-with-a-positive-toxin-test
#20
Julia Origüen, Laura Corbella, María Ángeles Orellana, Mario Fernández-Ruiz, Francisco López-Medrano, Rafael San Juan, Manuel Lizasoain, Tamara Ruiz-Merlo, Alejandra Morales-Cartagena, Guillermo Maestro, Patricia Parra, Jennifer Villa, Rafael Delgado, José María Aguado
OBJECTIVES: To evaluate the potential role of PCR-based assays in the overdiagnosis of Clostridium difficile infection (CDI) by using a validated diagnostic algorithm in daily clinical practice. METHODS: We performed a retrospective cohort study evaluating all C. difficile-positive stool samples identified at our institution during a 12-month period, to compare outcomes and recurrence rate between patients with a positive enzyme-immunoassay (EIA) for both glutamate dehydrogenase (GDH) and toxin A/B ("toxin-positive group"), with those with GDH-positive, toxin-negative samples in which the diagnosis was made by a positive PCR-based assay ("toxin-/PCR+ group")...
August 12, 2017: Clinical Microbiology and Infection
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