Clostridium difficile—associated diarrhea

American Family Physician,  March 1, 2005  by Michael S. Schroeder

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In patients with fulminant C. difficile-associated diarrhea, flexible sigmoidoscopy can provide an immediate diagnosis. (4,13) The finding of pseudomembranes is pathognomonic for C. difficile colitis (Figure 1). CT scanning also can diagnose fulminant disease quickly. When considered with the clinical history, the presence of ascites, colon wall thickening, or dilation can help categorize the severity of the colitis. (4)

Treatment

The treatment of C. difficile-associated diarrhea depends on the clinical presentation (Figure 3). (18) In otherwise healthy adults, the first step is to discontinue the precipitating antibiotic, if possible, and administer fluids and electrolytes to maintain hydration. With this conservative therapy, diarrhea can be expected to resolve in 15 to 23 percent of patients. (19)

Specific pharmacotherapy for C. difficile-associated diarrhea should be initiated in older patients, patients with multiple medical problems, and patients in whom antibiotics need to be continued. Specific treatment also should be initiated if diarrhea persists despite discontinuation of the precipitating antibiotic or if there is evidence of colitis (i.e., fever, leukocytosis, characteristic findings of colitis on CT scanning or endoscopy). (6) Use of opiates and antidiarrheal medications should be avoided or minimized because decreased intestinal motility can exacerbate toxin-mediated disease.

First-line therapy consists of metronidazole, 500 mg orally three or four times daily for 10 to 14 days. (20,21) Metronidazole is an inexpensive drug with a greater than 90 percent positive response rate (21) (Table 3). (13,19-21)

Vancomycin also is an effective treatment, with a response rate of greater than 90 percent. (21) If a patient is pregnant or does not respond to or tolerate metronidazole, vancomycin should be initiated in a dosage of 125 to 500 mg orally four times daily for 10 to 14 days. (6)

Response to therapy can be assessed by the resolution of fever, usually within the first two days. Diarrhea should resolve within two to four days. Treatment is continued for 10 to 14 days. Therapeutic failure is not determined until treatment has been given for at least five days. (19)

Twenty to 25 percent of patients with C. difficile infection will have recurrent infection. (6,9) Recurrence seldom is caused by treatment-resistant strains; usually, it is due to the germination of persistent C. difficile spores in the colon after treatment or to reinfection because of reingestion of the pathogen. (9) Management of recurrent C. difficile infections remains controversial, although most relapses respond to another course of antibiotics given in standard dosages for 10 to 14 days. Up to 5 percent of patients have more than six recurrences. (6)

In patients with recurrent C. difficile infection, enemas containing human stool have been used to restore normal microflora in the colon. This approach has had good response rates; however, the enemas are unwieldy to perform, and there is a risk of transmitting retroviruses or other infectious agents. (22) One potential benefit of enemas is a decrease in the use of vancomycin for recurrent C. difficile infections and therefore a theoretical decrease in the emergence of vancomycin-resistant bacteria.