Pseudomembranous antibiotic-associated colitis

Oral Staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis produced by C. difficile. The parenteral product may also be given orally for these infections. Oral vancomycin is not effective for other types of infection. 

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. 

Like penicillins, cephalosporins alter the normal microflora of the intestinal tract and can canse anorexia, nausea, vomiting, and diarrhea. In some cases the diarrhea can become severe enough to warrant discontinuation of the drug. Antibiotic-associated pseudomembranous colitis due to C. dijficile can also occur with the cephalosporins. This condition should be considered in the differential diagnosis of diarrhea associated with cephalosporin use. 

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)... 

Antimicrobial regimens used in eradication are not without risk for cases of antibiotic-associated (pseudomembraneous) colitis have resulted. 

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... 

Bartlett JG. Antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1979 l(3) 530-9. 

Pierce PF Jr, Wilson R, Silva J Jr, Garagusi VF, Rifkin GD, Fekety R, Nunez-Montiel O, Dowell VR Jr, Hughes JM. Antibiotic-associated pseudomembranous colitis an epidemiologic investigation of a cluster of cases. J Infect Dis 1982 145(2) 269-74. 

Van Ness MM, Cattau EL Jr. Fulminant colitis complicating antibiotic-associated pseudomembranous colitis case report and review of the clinical manifestations and treatment. Am J Gastroenterol 1987 82(4) 374-7. 

Ariano RE, Zhanel GG, Harding GK. The role of anion-exchange resins in the treatment of antibiotic-associated pseudomembranous colitis. CMAJ 1990 142(10) 1049-51. 

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. 

FIGURE 31-7. Sigmoidoscopic photograph revealing the light-raised lesions of antibiotic-associated pseudomembranous colitis. 

Altered bowel ehmination pattern related to antibiotic-associated pseudomembranous colitis... 

Bandmann HJ, Breit R (1973) The mafenide story. Br J Dermatol 89 219 Bartle WR, Saibil FG (1977) Antibiotic-associated pseudomembranous colitis. Can med Assoc J 116 162... 

Employed as the hydrochloride and administered by dilute intravenous injection, vancomycin is indicated in potentially life-threatening infections that cannot be treated with other effective, less toxic, antibiotics. Oral vancomycin is the drug of choice in the treatment of antibiotic-induced pseudomembranous colitis associated with the administration of antibiotics such as clindamycin and lincomycin (section 9.3). 

Pseudomembranous colitis (PMC) was first reported in 1893 and was associated with antibiotic therapy in 1955. Although described in the preantibiotic era, the incidence increasingly has been associated with antibiotic administration. C. difficile is thought to be the cause in 10% to 20% of patients experiencing antibiotic-associated diarrhea, 50% to 75% of those with antibiotic-associated colitis, and greater than 90% of those with antibiotic-associated pseudomembranous colits. It is also the most common cause of nosocomial diarrhea, infecting 16% to 20% of inpatients, one-third of whom are symptomatic. ... 

The problems of multiple prescribing in the elderly have been discussed in the context of a case of enalapril-associated dry cough misdiagnosed as pneumonia [34" ]. The prescribed antibiotics caused pseudomembranous colitis and an opioid-based syrup contributed to delirium. The authors drew attention to the effect of the prescribing cascade that can occur following the failure to identify an adverse drug reaction. 

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]. 

Surawicz CM Antibiotic-associated diarrhea and pseudomembranous colitis Are they less common with poorly absorbed antimicrobials Chemotherapy 2005 51(suppl 1 ) 81—89. 

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

Diarrhea associated with organisms that penetrate the intestinal mucosa (eg, toxigenic E. coii, Saimoneiia sp., Shigeiia,) and pseudomembranous colitis associated with broad-spectrum antibiotics. Antiperistaltic agents may prolong or worsen diarrhea. 

Pseudomembranous colitis Pseudomembranous colitis has occurred with the use of broad-spectrum antibiotics caused by overgrowth of Clostridia therefore, it is important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use. 

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. 

Pseudomembranous colitis, associated with the use of broad spectrum antibiotics... 

Adverse reactions. Heartburn, nausea and vomiting due to gastric irritation are common, and attempts to reduce this with milk or antacids impair absorption of tetracyclines (see below). Loose bowel movements occur, due to alteration of the bowel flora, and this sometimes develops into diarrhoea and opportunistic infection (antibiotic associated or pseudomembranous colitis) may supervene. Disorders of epithelial surfaces, perhaps due partly to vitamin B complex deficiency and partly due to mild opportunistic infection with yeasts and moulds, lead to sore mouth and throat, black hairy tongue, dysphagia and perianal soreness. Vitamin B preparations may prevent or arrest alimentary tract symptoms. 

Almost all antibacterial agents have been observed to cause diarrhea in a variable proportion of patients (114,115). The proportion depends not only on the antibiotic, but also on the clinical setting (in-patient/out-patient), age, race, and the definition of diarrhea. Severe colonic inflammation develops in a variable proportion of cases, and in some cases pseudomembranous colitis occurs (116-121). Since 1977, much evidence has accumulated that the most important causative agent in antibiotic-associated diarrhea is an anaerobic, Gram-positive, toxin-producing bacterium, C. difficile (122-124). 

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. 

Therapy consists of withdrawal of the antibiotic when diarrhea occurs and replacement of fluid and electrolyte losses. In less severe cases of antibiotic-associated diarrhea, no further treatment is needed. However, in patients with pseudomembranous colitis, a more intensive approach is usually required. When a toxic syndrome develops, fluid losses within the bowel can be very large. In these cases, a central venous line offers the chance to measure central venous pressure. Usually there is also loss of serum proteins and in some cases blood, which need appropriate replacement. In the rare cases with fulminant colitis and toxic megacolon, surgical intervention may be necessary (165,166). 

The most prominent adverse reaction of the lincosamides is diarrhea, which varies from mildly loose bowel movements to life-threatening pseudomembranous colitis (see monograph on Beta-lactam antibiotics). Almost all antimicrobial drugs have been associated with severe diarrhea and colitis however, lincomycin and clindamycin have been particularly incriminated. The incidence of clindamycin-induced diarrhea in hospital is 23%. Diarrhea resolves promptly after withdrawal in most cases. It seems to be dose-related and may result from a direct action on the intestinal mucosa. Severe colitis due to C. difficile is not dose-related and occurs in 0.01-10% of recipients. Clustering of cases in time and place suggests the possibility of cross-infection. Even low doses of clindamycin, in some cases after topical administration, can cause marked alterations in several intestinal functions related to bowel flora (23). There was reduced susceptibility of C. difficile to clindamycin in 80% of French isolates in 1997 (24). Lincomycin was among the antibiotics that were most often associated with the development of antibiotic-associated diarrhea in a Turkish study of 154 patients other associated antibiotics were azithromycin and ampicillin (25). 

Most common side effects include nausea, vomiting, diarrhea, pseudomembranous colitis, hypersensitivity reaction, and seizure. Bleeding manifestations have occurred in some patients receiving beta-lactam antibiotics. These reactions have been associated with abnormalities in clotting time, platelet aggregation, and prothrombin time. 

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