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Clostridium Difficile

Introduction

Clostridium difficile also known as "CDF/cdf", or "C. diff", is a species of Gram-positive bacteria of the genus Clostridium that causes diarrhea and other intestinal disease when competing bacteria are wiped out by antibiotics.

Clostridia are anaerobic, spore-forming rods (bacilli). C. difficile is the most serious cause of antibiotic-associated diarrhea (AAD) and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. The C. difficile bacteria, which naturally reside in the body, become overpopulated: The overpopulation is harmful because the bacterium releases toxins that can cause bloating, constipation, and diarrhea with abdominal pain, which may become severe. Latent symptoms often mimic some flu-like symptoms. Often, it can be cured simply by discontinuing the antibiotics responsible. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of C. difficile AAD have been reported in up to 20% of cases.

Bacteriology

Clostridia are motile bacteria that are ubiquitous in nature and are especially prevalent in soil. Under the microscope, clostridia appear as long, irregularly (often "drumstick" or "spindle") shaped cells with a bulge at their terminal ends. Under Gram staining, Clostridium difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. When stressed, the bacteria produce spores, which tolerate extreme conditions that the active bacteria cannot tolerate.( Barth 375)

C. difficile is a commensal bacterium of the human intestine in 2-5% of the population. Long-term hospitalization or residence in a nursing home within the previous year are independent risk factors for increased colonization. In small numbers, C. difficile does not result in significant disease. Antibiotics, especially those with a broad spectrum of activity, cause disruption of normal intestinal flora, leading to an overgrowth of C. difficile, which flourishes under these conditions. This can lead to pseudomembranous colitis (PMC), the generalized inflammation of the colon and the development of pseudomembrane, a viscous collection of inflammatory cells, fibrin, and necrotic cells. Pathogenic C. difficile strains produce several known toxins. The most well-characterized are enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhea and inflammation seen in infected patients, although their relative contributions have been debated. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases. Toxin A indcuses actin depolymerization by a mechanism correlated with a decrease in the ADP-ribosylation of the low molecular mass GTP-binding Rho proteins . Another toxin, binary toxin, has also been described, but its role in disease is not yet fully understood.

Antibiotic treatment of C. difficile infections can be difficult, due both to antibiotic resistance as well as physiological factors of the bacteria itself (spore formation, protective effects of the pseudomembrane). C. difficile is transmitted from person to person by the fecal-oral ...