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Clostridium Difficile Toxin

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https://www.readbyqxmd.com/read/28321156/current-knowledge-on-the-laboratory-diagnosis-of-clostridium-difficile-infection
#1
REVIEW
Adrián Martínez-Meléndez, Adrián Camacho-Ortiz, Rayo Morfin-Otero, Héctor Jesús Maldonado-Garza, Licet Villarreal-Treviño, Elvira Garza-González
Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28314071/epidemiology-risk-factors-and-outcome-of-clostridium-difficile-infection-in-heart-and-heart-lung-transplant-recipients
#2
Jackrapong Bruminhent, Kelly A Cawcutt, Charat Thongprayoon, Tanya M Petterson, Walter K Kremers, Raymund R Razonable
BACKGROUND: Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. METHODS: This is a retrospective study from 2004-2013. CDI was defined by diarrhea and a positive toxigenic Clostridium difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013)...
March 17, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28301919/clostridium-difficile-toxin-a-induces-reactive-oxygen-species-production-and-p38mapk-activation-to-exert-cellular-toxicity-in-neuronal-cells
#3
Peng Zhang, Ji Hong, I Na Yoon, Jin Ku Kang, Jae Sam Hwang, Ho Kim
Clostridium difficile releases two exotoxins, toxin A and toxin B, which disrupt the epithelial cell barrier in the gut to increase mucosal permeability and trigger inflammation with severe diarrhea. Many studies have suggested that enteric nerves are also directly involved in the progression of this toxin-mediated inflammation and diarrhea. C. difficile toxin A is known to enhance neurotransmitter secretion, increase gut motility, and suppress sympathetic neurotransmission in the guinea pig colitis model. Although previous studies have examined the pathophysiological role of enteric nerves in gut inflammation, the direct effect of toxins on neuronal cells and the molecular mechanisms underlying toxin-induced neuronal stress remained to be unveiled...
March 17, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28286992/cadazolid-for-the-treatment-of-clostridium-difficile
#4
Bradley T Endres, Eugénie Bassères, M Jahangir Alam, Kevin W Garey
Antibiotic development goals for CDI include potent antimicrobial effect against C. difficile, limited killing of host microbiota, potential effect on spores, and ability to interfere with toxin production. Cadazolid, a novel, non-absorbable hybrid antibiotic has many of these criteria. In phase I and II clinical trials, cadazolid was shown to be safe, well tolerated, and efficacious positioning itself as a potential future viable therapeutic option for CDI. Areas covered: This review provides an in-depth evaluation of the chemistry, microbiology, pharmacodynamics, pharmacokinetics, and clinical trial results for cadazolid...
March 13, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28286152/toxin-production-of-clostridium-difficile-in-sub-mic-of-vancomycin-and-clindamycin-alone-and-in-combination-with-ceftazidime
#5
Ebrahim Rezazadeh Zarandi, Shahla Mansouri, Nouzar Nakhaee, Farhad Sarafzadeh, Mohammad Moradi
Toxin production in Clostridium difficile (C. difficile) is a key process for induction of diarrhea. Several factors such as sub-MIC of antibiotics impact on toxin production. The aim of this research is investigation of sub-minimum inhibitory concentration (sub-MIC) of vancomycin (VAN), clindamycin (CLI) separately and in combination with ceftazidime (CAZ) on toxin production in C. difficile. About ∼10(6) colony forming units (CFU) from 18-h culture of C. difficile ATCC 9689 and clinical isolates A(+)/B(+)/CTD(-), were cultured anaerobically in the pre-reduced medium with appropriate concentration of separated and in combination antibiotics...
March 7, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28284851/clostridium-difficile-derived-membrane-vesicles-induce-the-expression-of-pro-inflammatory-cytokine-genes-and-cytotoxicity-in-colonic-epithelial-cells-in%C3%A2-vitro
#6
Asiimwe Nicholas, Hyejin Jeon, Gati Noble Selasi, Seok Hyeon Na, Hyo Il Kwon, Yoo Jeong Kim, Chi Won Choi, Seung Il Kim, Je Chul Lee
Clostridium difficile is the most common etiological agent of antibiotic-associated diarrhea in hospitalized and non-hospitalized patients. This study investigated the secretion of membrane vesicles (MVs) from C. difficile and determined the expression of pro-inflammatory cytokine genes and cytotoxicity of C. difficile MVs in epithelial cells in vitro. C. difficile ATCC 43255 and two clinical isolates secreted spherical MVs during in vitro culture. Proteomic analysis revealed that MVs of C. difficile ATCC 43255 contained a total of 262 proteins...
March 9, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28279860/inhibition-of-spore-germination-growth-and-toxin-activity-of-clinically-relevant-c-%C3%A2-difficile-strains-by-gut-microbiota-derived-secondary-bile-acids
#7
Rajani Thanissery, Jenessa A Winston, Casey M Theriot
The changing epidemiology of Clostridium difficile infection over the past decades presents a significant challenge in the management of C. difficile associated diseases. The gastrointestinal tract microbiota provides colonization resistance against C. difficile, and growing evidence suggests that gut microbial derived secondary bile acids (SBAs) play a role. We hypothesized that the C. difficile life cycle; spore germination and outgrowth, growth, and toxin production, of strains that vary by age and ribotype will differ in their sensitivity to SBAs...
March 6, 2017: Anaerobe
https://www.readbyqxmd.com/read/28274145/emerging-monoclonal-antibodies-against-clostridium-difficile-infection
#8
Séverine Péchiné, Claire Janoir, Anne Collignon
Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. Areas covered: Herein, the authors review the different assays performed with monoclonal antibodies against C. difficile toxins and surface proteins to treat or prevent primary or recurrent episodes of C...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28274126/-selection-of-laboratory-procedures-to-detect-toxigenic-by-the-2-step-method
#9
Yoko Tanino, Mai Kodama, Hiroomi Daicho, Yoshito Miyauchi, Towa Yasumoto, Yukiji Yamada, Noriko Kyotani, Satoko Kurahashi, Masaji Ushiyama, Takeshi Kimura, Toshiaki Komori, Yumiko Fujitomo, Masaki Nakanishi, Naohisa Fujita
The 2-step method is an algorithm to detect toxigenic Clostridium difficile. We herein compared the sensitivities and specificities of an enzyme immunoassay (toxin A/B-EIA), toxigenic culture (TC-EIA), Loop-Mediated Isothermal Amplification assay (LAMP), and Xpert C. difficile (Xpert) with the detection of the toxin B gene by a polymerase chain reaction (PCR). The results obtained showed that the sensitivities and specificities of toxin A/B-EIA, Xpert, TC-EIA, and LAMP were 30 and 100%, 87.2 and 100%, 97.5 and 89...
March 22, 2017: JARMAM: Journal of the Association for Rapid Method and Automation in Microbiology
https://www.readbyqxmd.com/read/28262711/whole-genome-sequences-of-three-clade-3-clostridium-difficile-strains-carrying-binary-toxin-genes-in-china
#10
Rong Chen, Yu Feng, Xiaohui Wang, Jingyu Yang, Xiaoxia Zhang, Xiaoju Lü, Zhiyong Zong
Clostridium difficile consists of six clades but studies on Clade 3 are limited. Here, we report genome sequences of three Clade 3 C. difficile strains carrying genes encoding toxin A and B and the binary toxin. Isolates 103 and 133 (both of ST5) and isolate 106 (ST285) were recovered from three ICU patients. Whole genome sequencing using HiSeq 2500 revealed 4.1-Mb genomes with 28-29% GC content. There were ≥1,104 SNP between the isolates, suggesting they were not of a single clone. The toxin A and B gene-carrying pathogenicity locus (PaLoc) of the three isolates were identical and had the insertion of the transposon Tn6218...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28242058/clostridium-difficile-infection-among-us-emergency-department-patients-with-diarrhea-and-no-vomiting
#11
Fredrick M Abrahamian, David A Talan, Anusha Krishnadasan, Diane M Citron, Ashley L Paulick, Lydia J Anderson, Ellie J C Goldstein, Gregory J Moran
STUDY OBJECTIVE: The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. METHODS: We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013)...
February 24, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28238427/development-of-a-non-radiolabeled-glucosyltransferase-activity-assay-for-c-difficile-toxin-a-and-b-using-ultra-performance-liquid-chromatography
#12
John W Loughney, Catherine Lancaster, Colleen E Price, Van M Hoang, Sha Ha, Richard R Rustandi
Clostridium difficile infection (CDI) is the leading cause of gastroenteritis-associated death in the United States. The major virulent factors of C. difficile are toxin A (TcdA) and toxin B (TcdB). Toxicity is mediated by the glucosyltransferase domains on TcdA and TcdB wherein a glucose is transferred from UDP-glucose to Ras homolog family member A (RhoA) receptor. This modification results in disruption of critical cell signaling events. Vaccination against these toxins is considered the best way to combat the CDI...
January 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28223147/comparative-performance-study-of-six-commercial-molecular-assays-for-rapid-detection-of-toxigenic-clostridium-difficile
#13
Yossi Paitan, Tamar Miller Roll, Amos Adler
OBJECTIVES: Rapid and accurate detection of C. difficile in stool impacts patient treatment and containment efforts. Detection of C. difficile toxin genes using nucleic acid amplification techniques (NAAT) is part of a multistep algorithm. Our objective was to directly compare the diagnostic accuracy and applicability of 6 commercial C. difficile NAAT assays. METHODS: In this study, 210 specimens were analysed in parallel by 6 commercial NAAT. Toxigenic culture was used as a reference method...
February 18, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28219893/toxin-positive-clostridium-difficile-latently-infect-mouse-colonies-and-protect-against-highly-pathogenic-c-difficile
#14
Lucie Etienne-Mesmin, Benoit Chassaing, Oluwaseyi Adekunle, Lisa M Mattei, Frederic D Bushman, Andrew T Gewirtz
OBJECTIVE: Clostridium difficile is a toxin-producing bacterium and a leading cause of antibiotic-associated disease. The ability of C. difficile to form spores and infect antibiotic-treated persons at low multiplicity of infection (MOI) underlies its large disease burden. However, C. difficile-induced disease might also result from long-harboured C. difficile that blooms in individuals administered antibiotics. DESIGN: Mice purchased from multiple vendors and repeatedly testing negative for this pathogen by quantitative PCR bloomed C...
February 20, 2017: Gut
https://www.readbyqxmd.com/read/28217744/effect-of-tcdr-mutation-on-sporulation-in-the-epidemic-clostridium-difficile-strain-r20291
#15
Brintha P Girinathan, Marc Monot, Daniel Boyle, Kathleen N McAllister, Joseph A Sorg, Bruno Dupuy, Revathi Govind
Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts normally protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB, are part of a pathogenicity locus, which also includes the tcdR gene that codes for TcdR, an alternate sigma factor that initiates transcription of tcdA and tcdB genes...
January 2017: MSphere
https://www.readbyqxmd.com/read/28216103/a-clostridioides-difficile-bacteriophage-genome-encodes-functional-binary-toxin-associated-genes
#16
Thomas Riedel, Johannes Wittmann, Boyke Bunk, Isabel Schober, Cathrin Spröer, Sabine Gronow, Jörg Overmann
Pathogenic clostridia typically produce toxins as virulence factors which cause severe diseases in both humans and animals. Whereas many clostridia like e.g., Clostridium perfringens, Clostridium botulinum or Clostridium tetani were shown to contain toxin-encoding plasmids, only toxin genes located on the chromosome were detected in Clostridioides difficile so far. In this study, we determined, annotated, and analyzed the complete genome of the bacteriophage phiSemix9P1 using single-molecule real-time sequencing technology (SMRT)...
February 17, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28216085/occurrence-of-clostridium-difficile-ribotype-027-in-hospitals-of-silesia-poland
#17
Małgorzata Aptekorz, Anna Szczegielniak, Barbara Wiechuła, Celine Harmanus, Ed Kuijper, Gayane Martirosian
Clostridium difficile is an important healthcare-associated pathogen, responsible for a broad spectrum of diarrheal diseases. The aim of this prospective study was to determine the occurrence of C. difficile infection (CDI), to characterize cultured C. difficile strains and to investigate the association of fecal lactoferrin with CDI. Between January 2013 and June 2014, 148 stool samples were obtained from adult diarrheal patients (C. difficile as a suspected pathogen) hospitalized in different healthcare facilities of 15 Silesian hospitals...
February 12, 2017: Anaerobe
https://www.readbyqxmd.com/read/28215602/clostridium-difficile-infection-in-acute-flares-of-inflammatory-bowel-disease-a-prospective-study
#18
Harry Sokol, Valérie Lalande, Cecilia Landman, Anne Bourrier, Isabelle Nion-Larmurier, Sylvie Rajca, Julien Kirchgesner, Philippe Seksik, Jacques Cosnes, Frédéric Barbut, Laurent Beaugerie
OBJECTIVES: Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. The aims of our study were to look for predictive factors of CDI in patients hospitalized for IBD flare and to evaluate a rapid testing strategy in this population. METHODS: Consecutive patients hospitalized for IBD flare in Saint-Antoine Hospital (Paris, France) were prospectively tested for CDI with a defined strategy involving rapid testing and reference methods...
January 30, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28213939/protective-antibodies-against-clostridium-difficile-are-present-in-intravenous-immunoglobulin-and-are-retained-in-humans-following-its-administration
#19
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
#20
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
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