What is the best antibiotic treatment for C.difficile-associated diarrhea?

The Hospitalist. 2009 March;2009(03):

March 1, 2009|The Hospitalist

Melissa L.P. Mattison, MD;Joseph Ming-Wah Li, MD

Case

An 84-year-old woman presents with watery diarrhea. She recently received a fluoroquinolone antibiotic during a hospitalization for pneumonia. Her temperature is 101 degrees, her heart rate is 110 beats per minute, and her respiratory rate is 22 breaths per minute. Her abdominal exam is significant for mild distention, hyperactive bowel sounds, and diffuse, mild tenderness without rebound or guarding. Her white blood cell count is 18,200 cells/mm3. You suspect C. difficile infection. Should you treat empirically with antibiotics and, if so, which antibiotic should you prescribe?

Overview

C. difficile is an anaerobic gram-positive bacillus that produces spores and toxins. In 1978, C. difficile was identified as the causative agent for antibiotic-associated diarrhea.1 The portal of entry is via the fecal-oral route.

Some patients carry C. difficile in their intestinal flora and show no signs of infection. Patients who develop symptoms commonly present with profuse, watery diarrhea. Nausea, vomiting, and abdominal pain also can be seen. Severe cases of C. difficile-associated diarrhea (CDAD) can present with significant abdominal pain and multisystem organ failure, with toxic megacolon resulting from toxin production and ileus.2 In severe cases due to ileus, diarrhea may be absent. Risk of mortality in severe cases is high, with some reviews citing death rates of 57% in patients requiring total colectomy.3 Risk factors for developing CDAD include the prior or current use of antibiotics, advanced age, hospitalization, and prior gastrointestinal surgery or procedures.4

Risk factors for developing CDAD include: antibiotic use, advanced age, hospitalization, and prior gastrointestinal surgery or procedures. Metronidazole and oral doses of vancomycin are the most common treatments.

The initial CDAD treatment involves removal of the agent that incited the infection. In most cases, this means discontinuation of an antimicrobial agent. Removal of the inciting agent allows restoration of the normal bowel flora. In mild CDAD cases, this may be sufficient therapy. However, most CDAD cases require treatment. Although many antimicrobial and probiotic agents have been used in CDAD treatment, metronidazole and vancomycin are the most commonly prescribed agents. There is an ongoing debate as to which should be considered the first-line agent.

KEY Points

C. difficile is readily spread due to its hardy spore form.
The elderly, those with prior antibiotic exposure, anyone with recent hospitalization, and those with altered bowel flora are susceptible to C. difficile-associated diarrhea (CDAD).
Metronidazole remains the mainstay for treatment of mild CDAD, due to cost and concerns about proliferation of vancomycin-resistant pathogens.
Treat severe CDAD with oral vancomycin.
Severe CDAD can be defined as any patient with two or more points on the following scale: One point each for temperature > 38.3 degrees Celsius; age > 60 years; albumin level < 2.5 mg/dL; or white blood cell count > 15K cells/mm3. Any patient with endoscopic evidence for pseudomembrane formation or admission to the ICU for CDAD treatment can be considered to have severe disease.

Additional Reading

Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006;145(10);758-764.
Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359(18);1932-1940.
Gerding DN, Muto CA, Owens RC Jr. Treatment of Clostridium difficile infection. Clin Infect Dis. 2008;46(Suppl 1):S32-42.

Review of the Data

Metronidazole and vancomycin have the longest histories of use and are the most studied agents in CDAD. Metronidazole is prescribed 250 mg four times daily (or 500 mg twice daily) for 14 days. It is reasonably tolerated, although it can cause a metallic taste in the mouth. Vancomycin is given 125 mg four times daily (or 500 mg three times daily) for 10 to 14 days. Unlike metronidazole, which can be given by mouth or intravenously, only oral vancomycin is effective in CDAD.