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Clostridium difficile–Associated Diarrhea and Colitis: A Significant Cause of Nosocomial Infection

The Hospitalist. 2005 September;2005(09):

Treatment

The first step in the management of C. difficile diarrhea and colitis is to discontinue the precipitating antibiotics if possible (10,12). Diarrhea resolves in approximately 15–25% of patients without specific anti–C. difficile therapy (14,15). Conservative management alone may not be indicated, however, in patients who are systemically ill or who have multiple medical problems, since it is difficult to predict which patients will improve spontaneously. If it is not possible to discontinue the precipitating antibiotic because of other active infections, the patient’s antibiotic regimen should be altered if possible to make use of agents less likely to cause CDAD (e.g., aminoglycosides, trimethoprim, rifampin, or a quinolone).

Antiperistaltic agents, such as diphenoxylate plus atropine (Lomotil), or loperamide (Imodium), and narcotic analgesics should be avoided because they may delay clearance of toxins from the colon and thereby exacerbate toxin-induced colonic injury or precipitate ileus and toxic dilatation (12,16). Specific therapy to eradicate C. difficile should be used in patients with initially severe symptoms and in patients whose symptoms persist despite discontinuation of antibiotic treatment. Although the diagnosis of C. difficile colitis should ideally be established before antimicrobial therapy is implemented, current ACG guidelines recommend that empiric therapy should be initiated in highly suggestive cases of severely ill patients (Table 3 on page 54) (12).

Currently, oral vancomycin or metronidazole, used for 7 to 10 days, are considered first-line therapy by most authors and current guidelines. Metronidazole at a dose of 250 mg 4 times daily is recommended by most authors and ACG guidelines as the drug of choice for the initial treatment of C. difficile colitis (12). These recommendations are largely based on efficacy, lower costs, and concerns about the development of vancomycin-resistant strains. Major disadvantages of metronidazole include a less desirable drug profile and contraindications in children and pregnant women.

Vancomycin, on the other hand, at a dose of 125 mg 4 times daily, is safe and well tolerated and achieves stool levels 20 times the required minimal inhibitory concentration for the treatment of C. difficile. Drawbacks to the use of vancomycin are cost and potential development of vancomycin-resistant strains. The current ACG guidelines consider vancomycin the drug of choice in severely ill patients and in cases in which the use of metronidazole is precluded.

Table 4. Metronidazole and Vancomycin Treatment for C. difficile Diarrhea

First Relapse

  • Confirm diagnosis
  • Symptomatic treatment if symptoms are mild
  • 10–14 day course of metronidazole or vancomycin

Second Relapse

  • Confirm diagnosis
  • Vancomycin taper
    • 125 mg every 6 h for 7 days
    • 125 mg every 12 h for 7 days
    • 125 mg daily for 7 days
    • 125 mg every other day for 7 days
    • 125 mg every 3 days for 7 days

Further Relapse

  1. Vancomycin in tapering dose as above plus cholestyramine 4 gm bid, or
  2. Vancomycin 125 mg qid and rifampin 600 mg bid for 7 days, or
  3. Therapy with microorganisms (probiotics) (e.g., Saccharomyces bouldardii* (live yeast) 500-mg capsule twice daily for 30 days in combination with metronidazole or vancomycin), or
  4. Intravenous immunoglobulin

Adapted from Linevsky JH, Kelly CP. Clostridium difficile colitis. Lamont JH,ed. Gastrointestinal Infections: Diagnosis and Management. New York: Marcel Dekker; 1997: 293-325.

*Currently undergoing FDA approved clinical trial in United States.