Regulation of toxins A and B has been widely studied for many years, and it is known that the tcdRregulator gene, present in the PaLoc, activates tcdAand tcdBtranscriptionally and also activates its own two promoters. A higher mortality rate was observed in patients infected with strains that produce all three toxins.
used a rabbit ileal loop model to investigate the binary toxin and concluded that the toxin contributes significantly to eliciting a non-haemorrhagic fluid response. A number of studies have indicated that strains that produce binary toxins usually cause severe CDI. Binary toxin acts on the actin cytoskeleton, producing microtubule-based protrusions on the surface of epithelial cells. This toxin is classified as an ADP-ribosyltransferase and is encoded by the cdtAgene (the enzymatic component) and the cdtBgene (the binding component). difficilestrains are capable of producing binary toxin. It has also been found that tcdCis expressed in the exponential growth phase of the bacterium, while the other genes are expressed in the stationary phase. These researchers have classified the tcdgenes in two groups, one comprising A, B, D and E, and the other comprising C (as tcdChas the opposite orientation). Hundsberger and collaborators reported that two of the LCT genes, tcdDand tcdC, act as positive and negative regulators, respectively. These toxins act as glycosyltransferases that modify Rho and Ras proteins within the intestinal epithelial cells and disrupt the actin cytoskeleton, causing loss of intercellular junctions and the severe secretory diarrhoea associated with CDI.
Toxins A and B were the first identified in this bacterium both are encoded by genes in the pathogenicity locus (PaLoc) and are included in the large clostridial toxins (LCT), a family known to modify small GTPases. Ĭlostridium difficilecan produce three toxins: A, B and binary toxin. Interestingly, the presence of diabetes mellitus has been associated with a decreased risk of CDI. Other investigators extend the time of influence of antibiotic treatment to 12 months and also include administration of proton pump inhibitors as a risk factor. showed that 96% of CDI cases had been exposed to anti-microbials about 14 days before the manifestation of diarrhoea, and all patients had received anti-microbial treatment about 3 months before. The most important risk factor for CDI is age, although the duration of hospitalization is also important, along with exposure to anti-microbial agents. Patients with CDI in these locations always present fever, abdominal pain, leucocytosis and a decrease in intestinal motility. Ĭolitis can affect any part of the colon but is commonly severest in the distal colon and rectum. CDI may also lead to complications such as dehydration, electrolyte disturbance, hypoalbuminemia, toxic megacolon, bowel perforation, hypotension, renal failure, systemic inflammatory response syndrome, sepsis and death. The most severe symptoms are leucocytosis and elevated serum creatinine levels. In case of more severe symptoms, the patient may present with fever, shock or hypotension and severe ileus with cessation of diarrhoea. Doctors should suspect CDI when the patient has three unformed or watery stools daily for 1 or 2 days. The most common symptom of CDI is watery (not bloody) diarrhoea accompanied by abdominal pain. The incidence also depends on the country considered, and within Europe, the rates are highest in Finland and Poland and lowest in Turkey, Bulgaria and in East European countries. The incidence of CDI in hospitals depends on the type of unit, and the rates are highest in haematology, gastroenterology and nephrology units. difficilein the hospital environment has become problematical. difficileproduces spores that are capable of resisting heat, desiccation, and chemical agents. One of the reasons for the increase in the incidence of CDI is that C.
However, the number of cases and the severity of these have increased in the last 20 years. Historically, CDI was not considered a severe disease. Clostridium difficileis widely distributed in the soil and in the intestinal tracts of animals, both of which are considered as reservoirs of the bacterium.
Clostridium difficileinfection can be acquired by person to person transmission, especially by the faecal-oral route, and it can also be acquired by environmental contamination. One of the most serious problems associated with CDI is recurrence of the disease. Nonetheless, the commonest manifestations are diarrhoea and PMC. difficileinfection (CDI) range from asymptomatic carriage to fulminant disease. difficileas an important cause of pseudomembranous colitis (PMC) associated with antibiotic use. Clostridium difficileis a Gram-positive, spore-forming anaerobic bacterium discovered in 1935 by Hall and O’Toole.
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