Clostridium Difficile Colitis 1

CLOSTRIDIUM DIFFICILE COLITIS - 1 Mechanism and Pathogenesis • The first step in development of C.diff colonization is disruption of the normal intestinal flora, usually by antibiotics or rarely, by anti-neoplastics or immunosuppressive drugs • Clinically significant strains produce 2 exotoxins; A and B that bind intestinal brush border receptors. • The toxins inactivate regulatory proteins of the actin cytoskeleton leading to disaggregation of polymerized actin, opening of gap junctions, cell rounding and subsequent cell death. • They toxins also induce release of inflammatory mediators and cytokines. Epidemiology • C.diff causes between 30,000 and 3,000,000 cases of diarrhea and colitis in the US every year. • It is the most common cause of nosocomial diarrhea adding up to 2 weeks to length of hospitalization at an additional cost of $6000-10,000 per case • It is the cause of approximately 25% of all antibiotic associated diarrhea. • The antibiotics most frequently associated with infection include clindamycin, ampicilin, amoxicillin and cephalosporins. Less common or rare medications include erythromycin, cisplatin and the sulfonamides. Prior use of vancomycin and metronidazole are also predisposing factors as well as therapy for active infection. • Incidence is low in the outpatient setting but increasing. Overall risk in the outpatient setting 6 weeks after a course of antibiotics is 6.7 per 100, 000 exposures and about 20,000 cases per year. Clinical Presentation Can range from just diarrhea to pseudomembranous colitis to fulminant colitis • Mild Disease: Presents with mild lower abdominal cramping pain. Endoscopy may reveal patchy or diffuse nonspecific colitis • Moderate Disease; Presents with fever, volume depletion, Nausea, anorexia, profuse diarrhea, abdominal distention and cramps. Labs will show moderate leukocytosis and fecal leukocytes. Endoscopy reveals the same results as mild disease. • Severe Disease: Usually presents with profuse diarrhea and severe abdominal pain. Patients have a high fever and appear toxic, peritoneal signs, volume depletion. Labs show marked leukocytosis and fecal leukocytes. Endoscopy may reveal adherent yellow plaques (pseudomembranes) that vary in diameter and may coalesce to cover large mucosal areas. • Fulminant colitis develops in 1-3% of patients with ileus, toxic megacolon, perforation and death. • Possible associated complications include hypoalbuminuria with anasarca and a reactive arthritis occurring 1-4 weeks after colitis develops in some patients. • 10-20% of patients will develop a recurrence despite high initial response to therapy. 182 Diagnosis • Labs: o Leukocytosis (usually about 12-20) with a left shift and fecal leukocytes (50-60% of cases) o It can be isolated by anaerobic stool culture but this is seldom used. o The most sensitive (94-100%) and specific (99%) test is a tissue culture assay for toxin B. However, test takes 1-3 days to complete and requires special facilities o ELSIA can be used to detect either toxin A or B in stool, Sensitivity is 71-94% and specificity is 92-98%. Test is rapid and easily available and is now used by most laboratories to make the diagnosis. • Endoscopy: o Reserved for special occasions e.g. when stool cultures cannot be obtained or when rapid diagnosis is necessary. Endoscopy should be used sparingly due to the increased risk of perforation. o Mild disease may show normal results on sigmoidoscopy. For more severe disease, see possible findings above. • Radiology: o These can assist in making the diagnosis. Abdominal plain films may reveal paralytic ileus or a dilated colon. o Abdominal CT may show a diffusely thickened or edematous colon. This, in addition to pericolonic stranding and ascites might suggest impending toxic colitis. Treatment • Steps in Medical Management (Mylonakis, et al) o Isolate the patient o Educate personnel on contact precautions. o If possible, discontinue inciting antibiotic and avoid anti-peristaltic or opiate drugs. This step might be sufficient for mild disease. o Confirm the diagnosis with a C.diff test. If results of first specimen are negative and diarrhea persists, 1-2 additional samples should be sent. o If clinically indicated (moderate to severe diarrhea, systemic symptoms, significant. leukocytosis), antibiotic therapy should be considered. If suspicion is high and patient is severely ill, empiric therapy can be started. o Oral metronidazole (flagyl)250mg QID or 500mg TID for 10-14 days is usually adequate o Oral Vancomcyin125mg QID for 10-14 days is indicated for those who cannot tolerate flagyl, who fail flagyl therapy or in pregnant women. o The first relapse can be treated with another 10-14 day course. o Therapy for multiple relapses has not been examined by randomized trials. A tapering course of flagyl or vancomycin for 4-6 weeks has been used. • Indications for Surgery (Longo, et al) o Surgical management is warranted in toxic and fulminant disease. A subtotal colectomy is usually performed. o Suspect if patients fail to responds to medical treatment within 3 days o Factors influencing development of severe colitis include: 183 Host immunity status e.g. Recent surgery, chemotherapy, transplantation, HIV/AIDS Virulence of C.diff strain Type and timing of antibiotics o Indications for surgery include: Complicated or severe cases of C.diff not responding to maximal medical therapy Toxic complications such as fulminant colitis, hemorrhage and perforation References • Mylonakis E, Ryan E et al. Clostridium difficile - Associated Diarrhea. Archives of Internal Medicine 161: 525-533, February 2001. • Longo WE, Mazuski JE et al. Outcome after Colectomy for Clostridium Difficile Colitis. Diseases of the Colon and Rectum 47: 1620-1626, September 2004. Abiola Fasina August 25, 2005 184