Pseudomembranous colitis from

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]. 

Abdominal pain, esophagitis, nausea, vomiting, diarrhea, skin rash, and blood dyscrasias may be seen with the use of the lincosamides. These drag s also can cause pseudomembranous colitis, which may range from mild to very severe Discontinuing the drag may relieve mild symptoms of pseudomembranous colitis. 

Like the other anti-infectives, bacterial or fungal superinfections and pseudomembranous colitis (see Chap. 7) may occur with the use of these drags. The administration of the aminoglycosides may result in a hypersensitivity reaction, which can range from mild to severe and in some cases can be life threatening. Mild hypersensitivity reactions may only require discontinuing the drug, whereas the more serious reactions require immediate treatment. 

Humans Hydrogen peroxide has been used as an enema or as a cleaning agent for endoscopes and may cause mucosal damage when applied to the surface of the gut wall. Hydrogen peroxide enteritis can mimic an acute ulcerative, ischaemic or pseudomembranous colitis, and ranges from a reversible, clinically inapparent process to an acute, toxic fulminant colitis associated with perforation and death (Bilotta and Waye, 1989). It is conceivable that anecdotal reports of exacerbation of IBD by iron supplementation (Kawai et al. 1992) are mediated by hydroxyl radical production by the Fenton reaction. 

PMC = Pseudomembranous colitis. Data were summarized from the references noted in the table. Some articles present disparate data. In general, a minor decrease in flora ... 

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. 

Pseudomembranous colitis Pseudomembranous coiitis has been reported with neariy aii antibacteriai agents, inciuding meropenem and may range in severity from miid to iife-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhea subsequent to the administration of antibacterial agents. 

Pseudomembranous colitis Pseudomembranous colitis has been reported with nearly all antibacterial agents, including aztreonam, and may range in severity from mild to life-threatening. 

IV, IM, and oral administration Risk for pseudomembranous colitis that may range from mild to severe or life-threatening. Reserve for use in serious infections only. 

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. 

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... 

An acute colitis, different from pseudomembranous colitis, was observed in five patients taking penicillin and penicillin derivatives (133). There was considerable rectal bleeding. The radiographic findings were those of ischemic colitis (spasm, transverse ridging, thumbprinting, and punctuate ulceration). On sigmoidoscopy and biopsy, the mucosa was normal, except for an inflammatory cell infiltration in one case. Conservative treatment resulted in rapid remission. 

The appearance of pseudomembranous colitis in clusters of patients (143-146) may explain the wide variation in occurrence, and suggests that the disease may result from cross-contamination among patients rendered susceptible by antibiotic treatment. This is especially true for epidemic outbreaks in hospitals, where the disease may be considered a nosocomial infection favored by serious illness, frequent and prolonged use of broad-spectrum antibiotics (especially cephalosporins), and poor compliance with the rules of hospital hygiene (147). In such an epidemic, a variable proportion of... 

Colonic stricture, similar to ileum diaphragm disease, developed in a patient during prolonged administration of modified-release diclofenac (12). Pseudomembranous colitis and colonic ulceration, with or without a diaphragm-like colonic stricture, have been reported (SEDA-16, 110) (SEDA-17, 109). Dispersible diclofenac is a formulation from which absorption is more rapid than... 

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). 

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. 

The reported incidence of diarrhea associated with the administration of clindamycin ranges from 2 to 20%. A number of patients (variously reported as 0.01 to 10%) have developed pseudomembranous colitis caused by the toxin from the organism C. difficile. This colitis is characterized by abdominal pain, diarrhea, fever, and mucus and blood in the stools. Proctoscopic examination reveals white-to-yellow... 

Adapted and reproduced, with permission, from Vesikari T et al Pseudomembranous colitis with recurring diarrhea and prolonged persistence of Clostridium difficile in a 10-year-old girl. Acta Paediatr Scand I984 73 135. 

Aside from mild or severe allergic reaction, the most commonly experienced cephalosporin toxicities are mild and temporary nausea, vomiting, and diarrhea associated with disturbance of the normal flora. Rarely, a life-threatening pseudomembranous colitis diarrhea associated with the opportunistic and toxin-producing anaerobic pathogen, Clostridium difficile, can be experienced. Rare blood dyscrasias, which can even include aplastic anemia, also are seen. Certain structural types (details below) are associated with prolonged bleeding times and an antabuse-like acute alcohol intolerance. 

Lincomycin is a natural product isolated from fermentations of Streptomyces lincolnensis var. lincolnensis. It is active against Gram-positive organisms, including some anaerobes. It is indicated for the treatment of serious infections caused by sensitive strains of streptococci, pneumococci, and staphylococci. It generally is reserved for patients who are allergic to penicillin because of the increased risk of pseudomembranous colitis (described below). It also serves as the starting material for the synthesis of clindamycin (by a Sn-2 reaction that inverts the R stereochemistry of the C-7 hydroxyl to a C-7 S-chloride). 

Pennington (1980) describes four patients ranging in age from 65 to 81 years with pseudomembranous colitis after repeated cotrimoxazole therapy for slight infections in the region of the respiratory system or of the urinary tract (Bartle and Saibil 1977). A further case was observed by Cameron and Thomas (1977). Bjar-NASON and Bjornsson (1981) report a case of esophageal ulcers after cotrimoxazole. 

Ulcerative colitis is a mucosal disease that primarily affects the rectum. It is typically left-sided or diffuse, and only rarely involves the right colon exclusively [64]. The mean wall thickness in Crohn disease is usually greater than in ulcerative colitis [65]. The halo sign, a low-attenuation ring in the bowel wall caused by deposition of submucosal fat, is seen more commonly in ulcerative colitis than in Crohn disease. Proliferation of mesenteric fat is almost exclusively seen in Crohn disease, whereas proliferation of perirectal fat is nonspecific and can result from Crohn disease, ulcerative colitis,pseudomembranous colitis, or radiation colitis [64]. Abscesses are almost exclusively found in Crohn disease and not in ulcerative colitis [62]. 

Topical clindamycin is widely used in the treatment of acne vulgaris. Approximately 5% clindamycin hydrochloride is absorbed systemically (Barza et al. 1982). The degree of absorption largely depends on the vehicle, ranging from 0.13% (acetone) to 13.92% (DMSO) (Franz 1983). Several cases of topical-clindamycin-associated diarrhea have been reported (Becker et al. 1981). Pseudomembranous colitis is a side effect of systemic administration of clindamycin. A case of pseudomembranous colitis has been reported after topical administration by Milstone et al. (1981). 

---