Pathogens>Bacteria>

MICROBIOLOGY

• Spore-forming, anaerobic, gram-positive rod.
• Produces toxins A & B, which bind to specific receptors in colon.
• Toxins attack Rho proteins, disrupting actin formation and causing cell death.
• Spores contaminate hands and hospital environment. Alcohol and other antiseptic hand rubs may be ineffective in killing spores. Hand-washing physically removes spores.
• New hypervirulent strain (REA group B1/PFGE type NAP1) produces higher levels of toxins A and B; associated with fluoroquinolone resistance, more severe disease, and higher mortality.

CLINICAL

• Infection usually nosocomially acquired during ABx therapy or within 1-2 mos of stopping ABx.
• Fluoroquinolones, clindamycin, cephalosporins, penicillins most commonly associated ABx; but even metronidazole, vancomycin, and some chemotherapeutic meds have been incriminated.
• Up to 1/3 of hospitalized HIV+ pts infected: 2/3 of infected pts are asymptomatic carriers who can spread infection to others. High infection rates probably result from frequent ABx use and hospitalization. C.difficile--associated diarrhea in HIV+ pts not more severe or less responsive to treatment.
• About 1/3 of infected pts have Sx: watery diarrhea, abd pain, fever, leukocytosis.
• Fulminant colitis (3% of cases) causes severe pain, distention, fever, chills. May lead to perforation, ileus, megacolon, and death.
• Gold standard for Dx is tissue Cx cytoxicity assay. Toxins in stool extract cause cell rounding. Neutralization w/ specific Ab establishes specificity. Sensitive and specific but expensive, slow (24-48 hr), and not generally available.
• Commercial ELISA to detect toxins quicker and easier. Specific but only 70-90% sensitive. Detection of toxin A and B preferred, since some cases caused by strains that only produce toxin B. Stool Cx is nonspecific: identifies both toxigenic and nontoxigenic strains.
• Sigmoidoscopy/colonoscopy may show normal colon in mild cases, nonspecific colitis, or pseudomembranes (raised yellow plaques). Contraindicated for perforation or toxic megacolon. (Use proctoscopy with minimal insufflation.)
• Abdominal x-ray: dilated colon >7 cm in diameter (toxic megacolon), free air (perforation), ileus.
• CT may show thickened bowel wall or nodules. Changes usually seen in colon only and not small bowel. Ascites may be present.

SITES OF INFECTION

• Colon: most common involved site
• Small intestine: rarely involved
• Extraintestinal disease: very rare - cellulitis, soft tissue infection, pericarditis, reactive arthritis.

TREATMENT

• Stop ABx if possible. Consider switching PCP prophylaxis from TMP-SMX to dapsone. If Sx resolve, no further Rx needed.
• For mild cases begin metronidazole 500 mg PO tid or 250 mg PO qid x 10d. (Reserve vancomycin, which is more expensive.)
• For severe illness, increased creatinine, WBC >20,000, or metronidazole-unresponsive disease, begin vancomycin 125-500 mg PO qid.
• If underlying ABx cannot be stopped, consider continuing metronidazole or vancomycin until 1 wk after ABx completed.
• PO therapy preferred. If PO treatment not possible, give metronidazole IV and/or vancomycin via enema or jejunal tube.
• Maintain normal volume status and electrolytes.
• Antimotility drugs (loperamide, diphenoxylate) contraindicated (increased risk of toxic megacolon).
• Monitor closely for complications: toxic megacolon, perforation, ileus. Danger signs: increasing WBC, elevated creatinine, elevated lactic acid.
• Colectomy (total) may be life-saving for fulminant colitis and should be considered before WBC >50,000 or lactate >5.

• 10-30% of pts relapse, usually within 2 wks of stopping metronidazole or vancomycin.
• May be due to spores in gut or to reinfection.
• Not associated with ABx resistance. First relapse: retreat w/ metronidazole or vancomycin (equally effective).
• Multiple relapses may respond to vancomycin taper, (allows spores to germinate and then be killed): 125 mg PO qid, bid, qd, qod (1 wk at each interval), followed by 125 mg q3d x 2 wks (6-wk total course).
• Other options: Saccharomyces boulardii (a yeast) or Lactobacillus strain GG to recolonize colon, cholestyramine to bind toxins, or IV gamma globulin to provide anti-toxin IgG.

Drug Comments

FOLLOW UP

• Do not routinely repeat toxin assay after treatment.
• Pts who relapse once are at risk for multiple relapses.
• If mild Sx recur after treatment, do not treat.
• If mod-severe Sx recur, repeat toxin assay and treat as above if positive.

• If severe diarrhea, fever, leukocytosis or abdominal distension persist, evaluate for toxic megacolon.
• Toxic megacolon can occur without diarrhea (pooling of stool in atonic bowel, isolated right sided colitis).
• Signs of an acute abdomen (decreased bowel sounds, tenderness, rebound, guarding) suggest perforation.
• Persistent diarrhea can cause protein-losing enteropathy w/ hypoalbuminemia, ascites and peripheral edema.

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Diarrhea
• Flucloxacillin
• Metronidazole
• Vancomycin