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Clostridioides Difficile Colitis

Author: Larry J. Copeland, MD

Editor: Peter F. Schnatz, DO

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Clostridioides difficile infection should be suspected as a cause of acute diarrhea, defined as 3 or more loose or watery stools in a 24-hour period, in patients who have had recent surgery or antibiotic use. Other symptoms may include lower abdominal pain and cramping, fever, nausea, anorexia, and leukocytosis. In more severe cases, pseudomembranous colitis may result, which can rarely progress to necrotizing colitis, toxic megacolon, and possible subsequent perforation with the need for colectomy. The condition can be fatal.

Symptoms often begin during antibiotic therapy or, rarely, up to 10 weeks afterward. Most cases occur within 2 weeks of initiating antibiotic therapy. The differential diagnosis includes both infectious and noninfectious causes of diarrhea. Risk factors for C difficile infection include extremes in age (very young or elderly patients), prolonged hospitalization, and living in a nursing home. C difficile infection most often results when antibiotics, including those commonly used in the perioperative period (eg, clindamycin, ampicillin, cephalosporins, and quinolones), disturb the colonic microbiome, resulting in overgrowth of the anaerobic organism C difficile. This organism produces a cytotoxin and an enterotoxin, which cause the diarrhea. Since C difficile infection can be transmitted from person to person, contact precautions, including use of gowns and gloves, should be implemented if C difficile colitis is suspected. Alcohol-based hand sanitizers do not kill C difficile spores, so health care workers should wash hands with soap and water before and after patient contact.  

The diagnosis is established by symptoms accompanied by positive laboratory testing for C difficile toxin or toxigenic C difficile organisms. Colonization is common, so only liquid stool samples should be sent for testing, as the test cannot distinguish between C difficile infection and asymptomatic carriage, which does not require treatment. Testing options include nucleic acid amplification tests to detect toxigenic strains and enzyme immunoassays for glutamate dehydrogenase antigen and/or toxins A and B. Importantly, C difficile toxin is unstable and degrades at room temperature and it may be undetectable within 2 hours of collection. If the specimen cannot be promptly tested, it should be refrigerated. Because stool culture may take several days, it is seldom used, although it remains the gold standard. 

Patients with suspected C difficile infection, especially if elderly, should be seen and evaluated for dehydration, shock, and surgical complications. Many of these patients require hospital admission for intravenous rehydration, evaluation, and correction of electrolyte imbalances. When patients exhibit severe disease, including severe abdominal pain and apparent ileus, imaging should be considered. Computed tomography of the abdomen and pelvis with oral and intravenous contrast, when not contraindicated, is preferred.

The first step in the treatment of C difficile colitis is discontinuation of the inciting antibiotic agent. If ongoing therapy is required for treatment of infection, it may be best to choose an agent not frequently implicated in antibiotic-associated C difficile colitis. Diarrhea resolves in many patients when the offending antibiotic is discontinued. Initial treatment with antidiarrheal agents is controversial. The initial treatment of choice is oral vancomycin (125 mg 4 times daily for 10 days). Importantly, intravenous vancomycin is not appreciably excreted into the colon and will have no effect. Oral fidaxomicin (200 mg twice daily for 10 days) is another first-line option. Metronidazole (500 mg orally 3 times daily for 10 days) is an alternative second-line agent. Follow-up stool testing for patients who are recovering or have become asymptomatic is not recommended, as results frequently remain positive for weeks after treatment. Recurrence is common (20% or more) and can be treated with extended courses of oral vancomycin or fidaxomicin. Patients with one recurrence are at risk for others. Probiotics may be beneficial as adjuvant therapy in recurrent disease. Fecal microbiota transplant may also be useful in patients with severe recurrent disease.

The best preventive measures include prudent use of antibiotics and effective hand hygiene.

Further Reading:

Centers for Disease Control and Prevention. FAQs for clinicians about C diff. Available at: Verified January 2020.

McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.


Initial Approval May 2012; Revised May 2015; Reaffirmed January 2017; Revised July 2018; Revised January 2020 and renamed from “Clostridium Difficile Colitis”; Revised September 2021; Reaffirmed May 2023.


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