Clostridium difficile infection medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Many persons will also be asymptomatic and colonized with Clostridium difficile. Treatment in asymptomatic patients is controversial, also leading into the debate of clinical surveillance and how it intersects with public health policy.

It is possible that mild cases do not need treatment.

Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis (CDC) is made to avoid frank sepsis or bowel perforation.

Medical Therapy

Three antibiotics are effective against C. difficile.

• Metronidazole 500mg orally three times daily is the drug of choice, because of superior tolerability, lower price and comparable efficacy. Metronidazole is taken up by the GI tract, unlike vancomycin. Some therefore recommend prescriptions of severe cases with vancomycin, to insure adequate levels. IV metronidazole 500 mg TID is also effective.
• Oral vancomycin 125 mg four times daily is second-line therapy, but is avoided due to theoretical concerns of converting intestinal flora into vancomycin resistant organisms. However, it is used in the following cases: severe C. difficile diarrhea (the duration of diarrhea is reduced to 3 versus 4.6 days with metronidazole; no response to oral metronidazole; the organism is resistant to metronidazole; the patient is allergic to metronidazole; the patient is either pregnant or younger than 10 years of age. Vancomycin must be administered orally because IV administration does not achieve gut lumen minimum therapeutic concentration.
• The use of linezolid may be considered too.

It has been known that drugs traditionally used to stop diarrhea worsen the course of C. difficile-related pseudomembranous colitis. Loperamide, diphenoxylate and bismuth compounds are indeed contraindicated, because slowing of fecal transit time is thought to result in extended toxin-associated damage. Cholestyramine, a powder drink occasionally used to lower cholesterol, is effective in binding both Toxin A and B, and slows bowel motility and helps prevent dehydration. The dosage can be 4 grams daily, to up to four doses a day: caution should be exercised to prevent constipation, or drug interactions, most notably the binding of drugs by cholestyramine, preventing their absorption. A last-resort treatment in immunosuppressed patients is intravenous immunoglobulin (IVIG).

Pseudomembranous colitis caused by C. difficile is treated with antibiotics, for example, vancomycin, metronidazole, bacitracin or fusidic acid.

Patients should be treated for 10-14 days, unless the inciting antibiotics can’t be discontinued, in which case metronidazole or vancomycin should be continued for a week or so after discontinuation of the inciting antibiotics. Failure to initially respond is typically not due to resistance, but may be due to misdiagnosis, noncompliance or other GI disease.

Up to 15-20% of patients will relapse after treatment, not typically due to resistant organisms. The exact mechanism has not been clarified; these patients often do not develop as prominent an antibody response, so immune mediated defects may be contributory. Relapse usually is within a few days of discontinued prescription, though may be as long as 30 days afterward. For relapse, patients should receive a second course of metronidazole for 14 days. For a second relapse, a C. diff titer should be checked to confirm the diagnosis, and then a third course of antibiotics should be with vancomycin. For patients with multiple relapses, some recommend a schedule of tapering vancomycin, from full dose down to 125 mg q3 days over the course of 6 weeks. Other potential prescriptions that are not commonly used include prescriptions with cholestyramine, which binds the toxin (but will also bind vancomycin), and attempts to repopulate the gut with organisms.

Fecal Bacteriotherapy

Fecal bacteriotherapy, a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.