Clostridium Difficile

Pathogenesis

• Infxn when nl colonic flora altered by abx (eg. clinda. P-lactams. quinolones) or chemoRx and Pt colonized by C. difficile (or its spores) w subsequent toxin release

• Toxin A + B • colon brush border — necrosis & inflammation — pseudomembranes

• New highly toxigenic strains -»t mort. & length of hosp. (esp in elderly, nejm 2005.3532442)

Clinical manifestations (spectrum)

• Asx colonization <3% in healthy adults; 15-21% in inpatients treated w abx

• Acute watery diarrhea (occ bloody) • mucus, often w lower abd pain, fever. Tit WBC

• Pseudomembranous colitis: above sx • pseudomembranes • bowel wall thickening

• Fulminant colitis (2-3%): toxic megacolon (colon dilatation -6 cm on KUB. colonic atony, systemic toxicity) and or bowel perforation

• Ddx: infectious colitis, ischemic colitis. IBD

Diagnosis

• Stool ELISA: detects toxin A and or B; fast (2 6 h); Se 90%

if high clinical suspicion and 1st test . consider repeating some ELISAs only detect A ( miss B-prod. strains)

• Stool cytotoxin assay: gold standard, highly Se & Sp; takes 24-48 h

Treatment <nejm 2002:346 334)

• Discontinue antibiotics as soon as possible; avoid antimotility agents

« Metronidazole 500 mg PO tid (1st choice) x 10-14 d; if need to stay on original abx. continue MNZ for >7 d post-abx cessation. IV MNZ w similar efficacy, should be used if I gut motility or absorption, or inability to tolerate POs; there is T'ing rate of MNZ resistance

• Vancomycin 125-500 mg PO qid >: 10-14 d; efficacy MNZ. but T cost; can select for VRE

indicated if diarrhea colitis severe. Pt pregnant or < 10 y. or no improvement w MNZ

• Recurrent C. difficile infection (15-30% of Pts) (Go«ro 2006.130:1311)

1st relapse: conservative Rx if sx mild; 14 d MNZ or vanco if mod severe 2nd relapse: PO vanco taper

Further relapses: prolonged vanco - S. boulardii or cholestyramine; ? IVIG

• Adjunctive Rx: Saccharomyces boulardii, lactobacillus. cholestyramine, fecal enemas

• Consider flex sig if dx uncertain and or evidence of limited improvement w standard Rx

• Stool carriage may persist 3-6 wks post-cessation of sx and should not trigger further Rx

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