Clostridium difficile

Lori Hamm, PharmD

Pediatr Pharm. 2000;6(6) 

In This Article

Treatment

The first treatment of C difficile infection should be to discontinue the causative antibiotic and allow the normal colonic flora to recover and the diarrhea to resolve. This approach alone has proven successful in approximately 15-25% of patients. In some patients, fluid and electrolyte replacement may also be necessary. With mild cases of C difficile infection (ie, diarrhea with minimal symptoms), patients should be monitored for 48 hours for symptomatic improvement before treatment with an antibiotic is instituted. However, patients with more serious infections suggested by symptoms of high fever, pronounced leukocytosis, severe abdominal pain, and absence of diarrhea, may require antibiotic therapy immediately.[2,9,13,14]

Vancomycin and metronidazole are the two primary antibiotics used in the treatment of C difficile infection.[1,2,3,6,7,9,10,11,12,13,14] A 7 to 10-day course of therapy is necessary with either agent in the treatment of C difficile infections.[3,14]

Oral metronidazole is the preferred oral agent of therapy.[3,6,13,14] Metronidazole is readily absorbed in the upper gastrointestinal tract, and although usually well tolerated, systemic side effects can occur.[1,2,3,6] Dosing recommendations for metronidazole are oral doses of 250-500 mg administered four times daily or 500-750 mg three times a day. If metronidazole is not tolerated orally, metronidazole can be given intravenously at a dose of 500-750 mg three or four times a day.[3,14] Possible side effects of metronidazole include an unpleasant metallic taste, nausea, vomiting, diarrhea, abdominal pain, headache, pruritus, erythematous rashes, dizziness, and reversible neutropenia.[1,2,3,6]

Vancomycin should be reserved for severe, life-threatening cases of C difficile infection, for patients unable to tolerate metronidazole, or for patients without symptom resolution after completing a course of metronidazole. Vancomycin is more expensive than metronidazole and the emergence of vancomycin-resistant enterococci is also a concern.[3,6,13,14] Oral vancomycin is not appreciably absorbed or metabolized, but is excreted in the stool unchanged, which is ideal for the treatment of C difficile infection. Intravenous vancomycin should not be used, however, since bactericidal concentrations are not achieved in the colon.[1,2,3,6] For vancomycin, oral doses of either 125 mg four times daily or 500 mg four times daily in adults are recommended. Both regimens have provided the same clinical outcome.[14,15] The use of a rectal vancomycin enema (500 mg diluted in 1000 mL of 0.9% sodium chloride injection) is an alternative as described in several anecdotal reports.[16]

In 1983, Teasley et al performed a small, prospective, randomized trial which showed oral metronidazole 250 mg administered every 6 hours to be equivalent to oral vancomycin 500 mg administered every 6 hours in the treatment of C difficile infection in adults. Response rates within six days of therapy were 98% with vancomycin and 93% with metronidazole, and eradication of C difficile after 21 days of completing therapy was 26% versus 40%, respectively.[15] Since then, other prospective, randomized comparisons have not shown significant differences between these two agents in the treatment of C difficile.[17,18,19]

In the pediatric population, oral metronidazole has not been compared to oral vancomycin in the treatment of C difficile infection. Recommended doses are 30-50 mg/kg/day divided every six hours for metronidazole and 40 mg/kg/day divided every six to eight hours for vancomycin. The oral vancomycin solution that is commercially available may prove to be more palatable than the extemporaneously prepared metronidazole suspension for children who are unable to swallow tablets.[4,14] In severe cases, a combination of intravenous metronidazole and oral vancomycin has been used.[20]

Alternative therapies for cases of mild C difficile infection include bacitracin, teicoplanin, or a binding resin such as cholestyramine or colestipol. However, these agents are not as reliable or as effective as vancomycin or metronidazole.[3,14] Approximately 10 to 20% of patients have a relapse of diarrhea from C difficile infection after an initial course of antibiotic therapy. Failure to eradicate the organism or reinfection is a possible reason for these recurrences. Recurrent episodes traditionally respond to the same ten-day course of antibiotic therapy used with the first episode. Management of repeated relapses is more difficult; suggested options include a slow tapering of vancomycin or metronidazole, the use of rifampin or cholestyramine, bacteriotherapy with oral administration of nontoxigenic C difficile, or treatment with the yeast Saccharomyces boulardii. Due to the lack of data, no formal therapeutic recommendation for multiple relapses can be made at this time.[1,2,3,10,11,14]

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