Recent advances in Clostridium difficile-associated disease

Institute of Infection, Immunity & Inflammation, University of Nottingham and Nottingham University Hospitals NHS Trust, UK.
Postgraduate medical journal (Impact Factor: 1.45). 04/2009; 85(1001):152-62. DOI: 10.1136/gut.2007.128157
Source: PubMed


The main purpose of this article is to review recent developments in the management of acute and recurrent Clostridium difficile-associated disease, with consideration of existing and new antibiotic and non-antibiotic agents for treatment. Details of the current developmental stage of new agents are provided and the role of surgery in the management of severe disease is discussed. Infection control measures considered comprise prudent use of antimicrobials, prevention of cross-infection and surveillance. Other topics that are covered include the recent emergence of an epidemic hypervirulent strain, pathogenesis, clinical presentation and approaches to rapid diagnosis and assessment of the colonic disease.

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Available from: Tanya Marie Monaghan, Feb 23, 2014
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    • "Host factors that may determine the development and nature of clinical disease are not fully understood but include age, the use of proton-pump inhibitors or H2 blockers, tube feeding and the host immune response [1,3,4,5,6]. Secreted toxins A and B mediate the intestinal disease [1,7] and serum IgG antibodies against toxin A appear to dominate protective responses in humans; more recently, antitoxin B responses have been correlated with colonization [3] and prevention of recurrent disease [8]. "
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    ABSTRACT: C. difficile infection (CDI) is rarely reported in cystic fibrosis (CF) patients despite frequent hospitalisations and antibiotic usage. Conversely, the prevalence of CDI in inflammatory bowel disease (IBD) has received increased attention. We investigated components of the IgG-specific humoral immune response to C. difficile toxins A and B in patients with C. difficile-associated diarrhoea (CDAD), IBD patients with CDI, CF patients and healthy controls. Serum anti-toxin IgG was determined by ELISA. Circulating antigen-activated B-cells were investigated using Alexa Fluor 488-labelled toxin A and assessed by flow cytometry. Following induction of differentiation of memory B-cells, toxin A- and B-specific antibody secreting cells (ASCs) were quantified using ELISpot. We present the first data showing levels of serum anti-toxin A and B antibodies were significantly higher in patients with CF (without a history of CDI) than in CDAD patients and were stably maintained over time. Notably, the CDAD patients were significantly older than the CF patients. We also show that circulating toxin A-specific memory B-cells (IgD-negative) can be detected in CDAD patients [0.92 (0.09-1.78)%], and were prominent (5.64%, 1.14%) in two CF patients who were asymptomatic carriers of C. difficile. There was correlation between toxin A- and B-specific ASCs, with significantly higher proportions of the latter seen. In some with CDAD, high serum antibody levels were seen to only one of the two toxins. Mucosal secretion of toxin-specific IgG was detected in an additional group of IBD patients with no history of CDI. We conclude that enhanced and stable humoral immune responses to toxins A and B may protect CF and some IBD patients against CDI. The impaired ability to generate strong and/or sustained toxin-specific antibody and memory B-cell responses may increase susceptibility of older patients to CDI and highlight the need to investigate the role of immune senescence in future studies.
    PLoS ONE 09/2013; 8(9):e74452. DOI:10.1371/journal.pone.0074452 · 3.23 Impact Factor
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    • "C. difficile associated colitis is known to lead to a superficial inflammation and is therefore ideally suited for CLE based analysis [20]. In fact, we were able to observe similar changes by CLE as compared to standard histopathology with high sensitivity, specificity and accuracy. "
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    ABSTRACT: Clostridium difficile infection (CDI) is one of the most dreaded causes of hospital-acquired diarrhea. Main objective was to investigate whether confocal laser endomicroscopy (CLE) has the capability for in vivo diagnosis of C. difficile associated histological changes. Second objective was to prove the presence of intramucosal bacteria using CLE. 80 patients were prospectively included, 10 patients were diagnosed with CDI based on toxigenic culture. To validate the presence of intramucosal bacteria ex vivo, CLE was performed in pure C. difficile culture; additionally fluorescence in situ hybridization (FISH) was performed. Finally, CLE with fluorescence labelled oligonucleotide probe specific for C. difficile was performed ex vivo in order to prove the presence of bacteria. CLE identified CDI-associated histological changes in vivo (sensitivity and accuracy of 88.9% and 96.3%). In addition, intramucosal bacteria were visualized. The presence of these bacteria could be proven by CLE with labeled, specific molecular C. difficile probe and FISH-technique. Based on comparison between CLE and FISH analyses, sensitivity and specificity for the presence of intramucosal bacteria were 100%. CLE has the potential for in vivo diagnosis of CDI associated colitis. In addition, CLE allowed the detection of intramucosal bacteria in vivo.
    PLoS ONE 03/2013; 8(3):e58753. DOI:10.1371/journal.pone.0058753 · 3.23 Impact Factor
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    • "For any individual patient with symptomatic CDI, the spectrum of disease can vary widely. While initial treatment is effective in most cases, some cases are highly complex including patients with recalcitrant or recurrent disease [1], infections caused by increasingly virulent strains of Clostridium difficile (C. difficile) that are unresponsive to traditional medical therapy [2] [3] [4], and patients with fulminant colitis requiring surgery [5] [6] [7] [8] [9] [10]. "
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    ABSTRACT: . Diagnosis and management of Clostridium difficile infection (CDI) rely upon clinical assessments and diagnostic studies. Among diagnostic tests, lower gastrointestinal (GI) endoscopy in the setting of CDI remains controversial. Objective . To describe the role of lower endoscopy in CDI management. Methods . Retrospective study of lower endoscopies in CDI at four metropolitan hospitals, July 2005 through December 2007. Results . Of 1760 CDI inpatients, 45 lower endoscopies were performed on 43 patients. Most common indications were ruling out other etiologies (42%), inconclusive stool studies (36%), and worsening course (11%). Most endoscopies (73%) had positive findings, including pseudomembranous colitis (49%) and nonspecific colitis (24%). Biopsies were performed in 31 cases, more with nonspecific colitis (10/11, 92%) compared to pseudomembranous colitis (14/22, 64%). Conclusion . While not recommended as a primary screening tool, lower GI endoscopy can add valuable information in CDI when other colonic pathologies may exist, studies are inconclusive, or clinical status worsens.
    Gastroenterology Research and Practice 10/2011; 2011(10):626582. DOI:10.1155/2011/626582 · 1.75 Impact Factor
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