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CLOSTRIDIUM DIFFICILE COLITIS - 1

I. Introductiona. Clostridium Difficile is a member of the Clostridia genus; spore-forming,

anaerobic, Gram-positive bacilli.b. Identified virulence factors of C. Difficile are Toxin A (enterotoxin) and Toxin B

(cytotoxin).c. Clinical presentation of C. Diff can range from a mild diarrhea to

Pseudomembranous Colitis with megacolon and perforation.

II. Epidemiology & Risk Factorsa. C. Diff is responsible for 15-25% of antibiotic-associated diarrhea and more than

95% of pseudomembranous colitis cases.

b. It has been identified as the leading cause of nosocomial infectious diarrhea inadults.

c. Asymptomatic carriage is observed in less than 3% of healthy adults.d. Mortality of patients requiring a colectomy for toxic megacolon or colonicperforation was high, ranging from 35-50%.

e. 90% of C. Diff infections occur after or during antibiotic treatment.f. The main risk factor is antimicrobial therapy up to 6 weeks prior to onset of signs

and symptoms. Classically, clindamycin has been emphatically correlated with

acquisition of C. Diff. However, because they are widely used, cephalosporinsare actually the most common antibiotics implicated. Except for

aminoglycosides, almost all antibiotics have been described for developing C.Diff

associated diarrhea.g. Other risk factors include: older age, antineoplastic chemotherapy, length of

hospital stay, NG tubes, enemas, recent GI surgery, and inflammatory boweldisease.

III. Pathogenicitya. Administration of broad spectrum antibiotics disrupts the natural bacterial gut

flora. Without competition from other organisms, the residing or introduced C.

Difficile thrives, multiplies, and produces Toxins A & B.

b. Toxin A & B are similar in that they both cause disruption of the actincytoskeleton and subsequent breakdown of the tight junction barrier betweencolonic epithelial cells.

c. There is an increase in the permeability of the colon which forms the basis of thewatery diarrhea.

d. Toxin A & B also induce production of TNF- and Interleukins, triggering andintensifying an inflammatory response.

e. Tissue necrosis and perhaps apoptosis are also effects of the toxins. Cellulardebris, extravasated neutrophils, and fibrin accumulate and form the characteristic

yellow-white plaques called pseudomembranes, which blanket the affected

colonic mucosa.

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IV. Laboratory Diagnosisa. Detection of C. Diff toxins in the stool by ELISA is a very quick and sensitive

test.

b. A more specific cytotoxicity test involves human cell culture exposed to theexotoxin and observation of cell death to confirm the diagnosis.

V. Treatmenta. Mild cases are treated with discontinuation of the precipitating antiiotic and

avoidance of antiperistaltic drugs.

b. More severe cases are treated with either Metronidazole (IV or PO) orVancomycin (PO).

c. In fulminant cases, colectomy may be required.d. Preventive measures requires a constant awareness of C. Diff infection. The first

step is prompt diagnosis followed by control of dissemination by implementingfull enteric precautions. To gain control of spread, segregation of patients to

private rooms with private toilet facilities, disinfection of patients surroundings,

and the promotion of hand-washing and use of gloves by hospital workers shouldbe instituted.

References:

1. Barbut F, Petit JC. Epidemiology of Clostridium Difficile-associated infections.

European Society of Clinical Microbiology and Infectious Diseases 2001; 7: 405-410.

2. Poxton IR, McCoubrey J, and Blair G. The Pathogenicity of Clostridium Difficile.

European Society of Clinical Microbiology and Infectious Diseases 2001; 7: 421-427.

3. Freiler JF, Durning SJ, and Ender PT. Clostridium Difficile Small Bowel Enteritis

Occuring after Total Colectomy. Clinical Infectious Diseases 2001; 33: 1429-31.

Rex Chung, MS3