Genetic risk factors for Clostridium difficile infection in ulcerative colitis.
Ashwin N. Ananthakrishnan,Emily C Oxford,Deanna D. Nguyen,Jenny Sauk,Vijay Yajnik,Ramnik J. Xavier +5 more
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TLDR
Patients with inflammatory bowel disease are at higher risk for Clostridium difficile infection and disruption of gut microbiome and interaction with the intestinal immune system are essential mechanisms for pathogenesis of both CDI and IBD.Abstract:
Summary
Background
Patients with inflammatory bowel disease (IBD) are at higher risk for Clostridium difficile infection (CDI). Disruption of gut microbiome and interaction with the intestinal immune system are essential mechanisms for pathogenesis of both CDI and IBD. Whether genetic polymorphisms associated with susceptibility to IBD are also associated with risk of CDI is unknown.
Aims
To use a well-characterised and genotyped cohort of patients with UC to (i) identify clinical risk factors for CDI; (ii) examine if any of the IBD genetic risk loci were associated with CDI; and (iii) to compare the performance of predictive models using clinical and genetic risk factors in determining risk of CDI.
Methods
We used a prospective registry of patients from a tertiary referral hospital. Medical record review was performed to identify all ulcerative colitis (UC) patients within the registry with a history of CDI. All patients were genotyped on the Immunochip. We examined the association between the 163 risk loci for IBD and risk of CDI using a dominant genetic model. Model performance was examined using receiver operating characteristics curves.
Results
The study included 319 patients of whom 29 developed CDI (9%). Female gender and pancolitis were associated with increased risk, while use of anti-TNF was protective against CDI. Six genetic polymorphisms including those at TNFRSF14 [Odds ratio (OR) 6.0, P-value 0.01] were associated with increased risk while 2 loci were inversely associated. On multivariate analysis, none of the clinical parameters retained significance after adjusting for genetics. Presence of at least one high-risk locus was associated with an increase in risk for CDI (20% vs. 1%) (P = 6 × 10−9). Compared to 11% for a clinical model, the genetic loci explained 28% of the variance in CDI risk and had a greater AUROC.
Conclusion
Host genetics may influence susceptibility to Clostridium difficile infection in patients with ulcerative colitis.read more
Citations
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Journal ArticleDOI
Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment.
TL;DR: The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.
Journal ArticleDOI
Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis.
TL;DR: Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted–CDI clinical management procedures, prevention, and research.
Patent
Microbiota restoration therapy (mrt), compositions and methods of manufacture
TL;DR: In this paper, a method for manufacturing a microbiota restoration therapy composition may include collecting a human fecal sample and adding a diluent to the human faecal sample to form a diluted sample.
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Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases.
Ashwin N. Ananthakrishnan,Andrew Cagan,Vivian S. Gainer,Su-Chun Cheng,Tianxi Cai,Peter Szolovits,Stanley Y. Shaw,Susanne Churchill,Elizabeth W. Karlson,Elizabeth W. Karlson,Shawn N. Murphy,Isaac S. Kohane,Isaac S. Kohane,Isaac S. Kohane,Katherine P. Liao,Katherine P. Liao +15 more
TL;DR: In this paper, a multivariate logistic regression model was used to identify independent effect of plasma 25(OH)D on risk of clostridium difficile infection (CDI).
Journal ArticleDOI
Ulcerative Colitis Patients With Clostridium difficile are at Increased Risk of Death, Colectomy, and Postoperative Complications: A Population-Based Inception Cohort Study.
Maria Negron,Ali Rezaie,Herman W. Barkema,Kevin P. Rioux,Jeroen De Buck,Sylvia Checkley,Paul L. Beck,Matthew W Carroll,Richard N. Fedorak,Levinus A. Dieleman,Remo Panaccione,Subrata Ghosh,Gilaad G. Kaplan +12 more
TL;DR: Clostridium difficile diagnosis worsens the prognosis of newly diagnosed patients with UC by increasing the risk of colectomy, postoperative complications, and death.
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A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.
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TL;DR: A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak ofC.difficile-associated diarrhea.
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Clostridium difficile Infection
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