Pseudomembranous colitis Clostridium difficile

Burke GW, Wilson ME, Mehrez lO. Absence of diarrhea in toxic megacolon complicating Clostridium difficile pseudomembranous colitis. Am J Gastroenterol 1988 83(3) 304-7. 

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]. 

Vancomycin (Vancocin) acts against susceptible gram-positive bacteria by inhibiting bacterial cell wall synthesis and increasing cell wall permeability. This drug is used in the treatment of serious gram-positive infections that do not respond to treatment with other anti-infectives. It also may be used in treating anti-infective-associated pseudomembranous colitis caused by Clostridium difficile. 

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

Pseudomembranous colitis (PMC) results from toxins produced by Clostridium difficile. It occurs most often in epidemic fashion and affects high-risk groups such as the elderly, debilitated patients, cancer patients, surgical patients, any patient receiving antibiotics, patients with nasogastric tubes, or those who frequently use laxatives. 

TcdB Clostridium difficile AB Rho-GTPases Rho-signaling disturbed Pseudomembranous colitis... 

Amoxicillin is a broad spectrum penicillin antibiotic. Antibiotics tend to cause pseudomembranous colitis as a result of colonisation of the colon by Clostridium difficile following antibiotic therapy. 

Pseudomembranous colitis/staphylococcal enterocolitis caused by Clostridium difficile-The parenteral form may be administered orally parenteral use alone is unproven. The oral use of parenteral vancomycin is not effective for other infections. 

Clindamycin can be administered orally with a high bioavailability. Also formulations for intravenous administration exist. Protein binding is about 90%. It is distributed throughout the body except the CNS. It shows excellent penetration in bone and in empyema and abscesses. It is metabolized in the liver and excreted in the bile. The elimination half-life is about 3 h. Adverse effects include gastrointestinal distress, skin rashes and decreased liver function. Pseudomembranous colitis is relatively frequently seen due to resistance of Clostridium difficile. 

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. 

Staphylococcal enterocolitis, ID-antibacterial-associated pseudomembranous colitis caused by Clostridium difficile PO 0.5-2 g/day in 3-4 divided doses for 7-10 days. Dosage in renal impairment After a loading dose, subsequent dosages and frequency are modified based on creatinine clearance, the severity of the infection, and the serum concentration of the drug. 

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. 

Penicillins alter the normal bacterial flora in areas of the body, including the respiratory and intestinal tracts. Patients taking oral penicillins may experience nausea, vomiting, or diarrhea. This is usually of little clinical significance because the normal microflora reestablishes itself quickly after cessation of therapy. However, serious superinfection with resistant organisms such as Pseudomonas, Proteus, or Candida can follow long-term therapy with any penicillin. Superinfection with Clostridium difficile can lead to potentially fatal pseudomembranous colitis. 

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... 

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. 

Levofloxacin can cause pseudomembranous colitis due to Clostridium difficile (19). 

Histologically confirmed pseudomembranous colitis has been reported in patients taking rifampicin. Bacteriology showed mainly Clostridium difficile resistant to rifampicin and several other antibiotics. Withdrawal of rifampicin and the use of vancomycin has been helpful (SEDA-6, 275) (SEDA-7, 310) (51). 

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. 

Pseudomembranous colitis—Inflammation of the colon caused by the toxin of Clostridium difficile and resulting in bloody diarrhea. 

Answer E. Vancomycin is usually considered to be a backup drug to metronidazole in colitis due to Clostridium difficile on the grounds that it is no more effective, is more costly, and should be reserved for treatment of resistant gram-positive coccal infections. None of the other drugs has activity in pseudomembranous colitis—indeed, they may cause it ... 

Gurian, L., Ward, T. T., and Katon, R. M. (1982). Possible foodborne transmission in a case of pseudomembranous colitis due to Clostridium difficile Influence of gastrointestinal secretions on Clostridium difficile infection. Gastroenterology 83, 465 69. 

This condition is caused by the organism Clostridium difficile. Because this organism is less responsive than others to the actions of penicillin, it proliferates in the intestine as other populations of bacteria are killed by the drug. It thus gives rise to pseudomembranous colitis. 

Metronidazole is used increasingly as primary therapy for pseudomembranous colitis due to Clostridium difficile infection. At doses of250-500 mg orally three times daily for 7-14 days, metronidazole is effective and less expensive than oral vancomycin. Metronidazole also is used in patients with Crohn s disease who have perianal fistulas or significant colonic disease fsee Chapter 38). 

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