Antibiotic-associated pseudomembranous colitis, Clostridium difficile

Antibiotic-associated diarrhea Pseudomembranous colitis Clostridium difficile Rifaximin Clostridium difficile-assodated diarrhea... 

Vancomycin is not absorbed after oral administration and must be given intravenously. Oral administrations are used for intraluminal gastrointestinal infections such as antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. Vancomycin is widely distributed in the body but does not cross the blood brain barrier and does not penetrate into bone. It is excreted mainly via the urine, resulting in accumulation in patients with renal insufficiency. Its elimination half-life is 4-11 hours but can increase to 6-10 days in renal failure. 

The most serious adverse effect is antibiotic-associated (pseudomembranous) colitis (see p. 210) usually due to opportunistic infection of the bowel with Clostridium difficile which produces an entero-toxin clindamycin should be stopped if any diarrhoea occurs. 

Antibiotic-associated pseudomembraneous colitis (caused by Clostridium difficile)... 

Antimicrobials are the commonest drugs that cause diarrhoea, probably due to alteration of bowel flora. It may range from a mild inconvenience to life-threatening antibiotic-associated (pseudomembranous colitis), due to colonisation of the bowel with Clostridium difficile. The condition particularly affects... 

Vancomycin is an antibiotic used to treat Staphylococcus and Clostridium difficile.These bacteria infect bones and joints and cause endocarditis and enterocolitis. Vancomycin is commonly prescribed to patients who are susceptible to endocarditis to prevent this infection from occurring. Vancomycin is particularly successful in treating methicillin-resistant strains of bacteria. However, parenteral vancomycin is not used to treat antibiotic-associated pseudomembranous colitis. 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

Clostridium difficile is a commensal Gram-positive anaerobic bacterium of the human intestine, found in about 2-5% of the population. C. difficile is the most serious cause of antibiotic-associated diarrhoea and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. The bacterium produces several known toxins, including enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhoea and inflammation seen in infected patients another toxin, binary toxin, has also been described. 

Clostridium difficile has been isolated in 11-33% of patients with antibiotic-associated diarrhea, 60-75% of patients with antibiotic-associated colitis, and 96-100% of patients with pseudomembranous colitis (117,134,135). However, about 2% of the adult population are asymptomatic carriers (127). Primary symptomless colonization with C. difficile reduces the risk of antibiotic-associated diarrhea (136). Infants up to 2 years seem to be refractory to pseudomembranous colitis, although a high percentage may be carriers of C. difficile (135,137). The reasons for this are unknown. It has been speculated that infants lack receptors for the toxin. 

Teicoplanin is an antibiotic agent used in the prevention and the treatment of serious infections caused by gram-positive bacteria. It is a semis5mthetic glycopeptide antibiotic with a spectrum of activities similar to vancomycin. Teicoplanin is marketed by Sanofi Aventis Corp. as Targocid . The oral adnunistration of teicoplanin is effective in the treatment of Pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with a comparable efficacy to vancomycin. The effectiveness of teicoplanin and its structure effect on treatment has been reviewed (50). The effect of teicoplanin is directly related to the length of its carbon chain. 

---