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Clostridium Difficile Toxin

Orsolya Benedek, Andreas Podbielski, Philipp Warnke
BACKGROUND: Chemiluminescent or enzyme-linked fluorescent immunoassays are commonly used to diagnose Clostridium difficile-associated diarrhea. METHODS: The LIAISON analyzer (DiaSorin, Italy) was compared to miniVIDAS (bioMérieux, France) and, furthermore, to culture of toxigenic strains. In total, 249 native stool samples were analyzed. Sensitivities, specificities, and positive and negative predictive values were investigated. Furthermore, performance under routine conditions was assessed...
September 29, 2016: European Journal of Microbiology & Immunology
Mária Džunková, Giuseppe D'Auria, Hua Xu, Jun Huang, Yinghua Duan, Andrés Moya, Ciarán P Kelly, Xinhua Chen
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials...
2016: Frontiers in Cellular and Infection Microbiology
Robert J Gianotti, Alan C Moss
Clostridium difficile (CD) is an anaerobic, spore-forming bacillus that is responsible for a spectrum of gastrointestinal illness ranging from asymptomatic carriage to toxic megacolon and death. The prevalence of CD infection is increasing in both hospitalized and community-based inflammatory bowel disease populations. Standard antibiotic therapy fails to cure or prevent recurrence in more than 50% of patients, thus increasing the need for alternative therapies. Recently, fecal microbiota transplantation has received renewed attention as a therapy for refractory or recurrent CD infection...
November 2016: Inflammatory Bowel Diseases
Jessica Martin, Mark Wilcox
PURPOSE OF REVIEW: Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of C. difficile infection (CDI) are undergoing clinical trials. RECENT FINDINGS: Bezlotoxumab is a monoclonal antibody against toxin B that has successfully completed phase III studies, demonstrating a significant reduction in recurrent CDI when given with standard of care antibiotics...
October 7, 2016: Current Opinion in Infectious Diseases
Karen Michael, David No, Jennifer Dankoff, Kyoyi Lee, Elisabeth Lara-Crawford, Marilyn C Roberts
Clostridium difficile is both a hospital and community acquired pathogen. The current study determined if C. difficile could be cultured from clinical laundry facility surfaces. A total of 240 surface samples were collected from dirty areas (n = 120), which handle soiled clinical linens, and from clean areas (n = 120), which process and fold the clean linens, within the University of Washington Consolidated Laundry facility in 2015. Sampling was done four times over the course of one year. The dirty area was significantly more contaminated than the clean area (21% vs 2%, p<0...
October 14, 2016: FEMS Microbiology Letters
Michele Chu, Michael J G Mallozzi, Bryan P Roxas, Lisa Bertolo, Mario A Monteiro, Al Agellon, V K Viswanathan, Gayatri Vedantam
Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis. Cell wall glycopolymers (CWGs) influence the virulence of various pathogens. Five C. difficile CWGs, including PSII, have been structurally characterized, but their biosynthesis and significance in C. difficile infection is unknown. We explored the contribution of a conserved CWG locus to C...
October 2016: PLoS Pathogens
Abdel-Naser Elzouki
Probiotics are live, nonpathogenic bacteria capable of colonizing the colonic mucosa. The most common probiotics include strains of Lactobacillus or Bifidobacteria, which are part of the normal gastrointestinal microbiota. Initial studies of selected probiotic species have suggested potential efficacy in several gastrointestinal diseases including inflammatory bowel diseases (particularly pouchitis), antibiotic-related diarrhea, Clostridium difficile toxin-induced colitis, infectious diarrhea, irritable bowel syndrome, and allergy...
November 2016: Journal of Clinical Gastroenterology
Leonie Schnell, Ann-Katrin Mittler, Andrea Mattarei, Domenico Azarnia Tehran, Cesare Montecucco, Holger Barth
Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA) from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA) has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT)...
July 15, 2016: Toxins
Deirdre L Church
Alteration in the host microbiome at skin and mucosal surfaces plays a role in the function of the immune system, and may predispose immunocompromised patients to infection. Because obligate anaerobes are the predominant type of bacteria present in humans at skin and mucosal surfaces, immunocompromised patients are at increased risk for serious invasive infection due to anaerobes. Laboratory approaches to the diagnosis of anaerobe infections that occur due to pyogenic, polymicrobial, or toxin-producing organisms are described...
August 2016: Microbiology Spectrum
Fabrizio Barbanti, Patrizia Spigaglia
Recent surveys indicate that the majority of toxigenic Clostridium difficile strains isolated in European hospitals belonged to PCR-ribotypes (RTs) different from RT 027 or RT 078. Among these types, RT 018 has been reported in Italy and, more recently, in Korea and Japan. In Italy, strains RT 018 have become predominant in the early 2000s, whereas the majority of strains isolated before were RT 126, a type belonging to the same lineage as the RT 078. In this study, we have found that Italian strains RT 018 are resistant to erythromycin, clindamycin, moxifloxacin and rifampicin...
October 7, 2016: Anaerobe
Daniel E Freedberg, Hojjat Salmasian, Bevin Cohen, Julian A Abrams, Elaine L Larson
Objective: To assess whether receipt of antibiotics by prior hospital bed occupants is associated with increased risk for CDI in subsequent patients who occupy the same bed. Design, Setting, and Participants: This is a retrospective cohort study of adult patients hospitalized in any 1 of 4 facilities between 2010 and 2015. Patients were excluded if they had recent CDI, developed CDI within 48 hours of admission, had inadequate follow-up time, or if their prior bed occupant was in the bed for less than 24 hours...
October 10, 2016: JAMA Internal Medicine
Avnish Kumar Seth, Pawan Rawal, Ruchika Bagga, Priti Jain
Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative...
September 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Manli Y Davis, Husen Zhang, Lera E Brannan, Robert J Carman, James H Boone
BACKGROUND: Clostridium difficile is the most common known cause of antibiotic-associated diarrhea. Upon the disturbance of gut microbiota by antibiotics, C. difficile establishes growth and releases toxins A and B, which cause tissue damage in the host. The symptoms of C. difficile infection disease range from mild diarrhea to pseudomembranous colitis and toxic megacolon. Interestingly, 10-50 % of infants are asymptomatic carriers of C. difficile. This longitudinal study of the C. difficile colonization in an infant revealed the dynamics of C...
October 7, 2016: Microbiome
L A Loza Vargas, Henar Núñez Rodríguez, Marina Benito Sanz, Tomás Zamora Martínez, Pilar Díez Redondo, Manuel Pérez Miranda
An 82-year-old male with a history of high blood pressure, COPD, chronic myeloid leukemia, and stage-4 chronic renal failure. Admitted to hospital for lower-limb cellulitis and severe COPD exacerbation, he received antibiotic therapy and bronchodilators. During his hospital stay he developed severe anemia and had an hematochezia event with no diarrhea. A complete colonoscopy found small (4-7 mm) nacreous elevated lesions, circumferential in shape, in the cecum and ascending colon with some bleeding stigmata and submucosal bleeding suggestive of infectious colitis; stool culture was negative and Clostridium difficile toxins were positive...
October 2016: Revista Española de Enfermedades Digestivas
B Kullin, J Wojno, V Abratt, S J Reid
The molecular epidemiology of C. difficile strains causing disease in South Africa is currently unknown. Previously, multidrug resistant ribotype (RT)017 strains were those most commonly isolated from patients with diarrhoea attending Groote Schuur Hospital in Cape Town, South Africa. This larger study aimed to investigate the molecular epidemiology and antibiotic susceptibility profiles of C. difficile strains in the greater Cape Town and regional areas. C. difficile strains were isolated from patients with diarrhoea attending hospitals in the Western Cape region of South Africa that tested positive using the GeneXpert CDiff diagnostic test...
September 30, 2016: European Journal of Clinical Microbiology & Infectious Diseases
Heike Stier, Stephan C Bischoff
BACKGROUND: The probiotic Saccharomyces boulardii CNCM I-745 (also known as Saccharomyces cerevisiae HANSEN CBS 5926; in the following S. boulardii) has proven its effectiveness in preventive and therapeutic treatment of many gastrointestinal diseases, especially diseases associated with acute diarrhea. In particular, antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, traveller's diarrhea, as well as acute diarrhea due to common viral and bacterial infections in children and adults...
2016: Clinical and Experimental Gastroenterology
Elena A Usacheva, Jian-P Jin, Lance R Peterson
Clostridium difficile infection (CDI) is a significant healthcare concern worldwide, and C. difficile is recognised as the most frequent aetiological agent of infectious healthcare-associated diarrhoea in hospitalised adult patients. The clinical manifestation of CDI varies from self-limited diarrhoea to life-threatening colitis. Such a broad disease spectrum can be explained by the impact of host factors. Currently, a complex CDI aetiology is widely accepted, acknowledging the interaction between bacteria and the host...
September 20, 2016: Journal of Global Antimicrobial Resistance
Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B Stallcup, Ji Miao, Xi He, Julian G Hurdle, David T Breault, Abraham L Brass, Min Dong
Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium...
September 28, 2016: Nature
Joseph P Zackular, Jessica L Moore, Ashley T Jordan, Lillian J Juttukonda, Michael J Noto, Maribeth R Nicholson, Jonathan D Crews, Matthew W Semler, Yaofang Zhang, Lorraine B Ware, M Kay Washington, Walter J Chazin, Richard M Caprioli, Eric P Skaar
Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI...
September 26, 2016: Nature Medicine
Karin Johansson, Hanna Karlsson, Torbjörn Norén
Diagnostic testing for Clostridium difficile infection (CDI) has, in recent years, seen the introduction of rapid dual-EIA (enzyme immunoassay) tests combining species-specific glutamate dehydrogenase (GDH) with toxin A/B. In a prospective study, we compared the C. DIFF Quik Chek Complete test to a combination of selective culture (SC) and loop-mediated isothermal amplification (LAMP) of the toxin A gene. Of 419 specimens, 68 were positive in SC including 62 positive in LAMP (14.7%). The combined EIA yielded 82 GDH positives of which 47 were confirmed toxin A/B positive (11%) corresponding to a sensitivity and specificity of 94% for GDH EIA compared to SC and for toxin A/B EIA a sensitivity of 71% and a specificity of 99% compared to LAMP...
November 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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