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Clostridioides (Clostridium) Difficile Colitis

Practice Essentials

Clostridioides difficile (formerly Clostridium difficile) colitis results from a disturbance of the normal bacterial flora of the colon, colonization by C difficile, and the release of toxins that cause mucosal inflammation and damage. Antibiotic therapy is the key factor that alters the colonic flora. C difficile infection (CDI) occurs primarily in hospitalized patients.

Signs and symptoms

Symptoms of C difficile colitis often include the following:

Mild to moderate watery diarrhea that is rarely bloody

Cramping abdominal pain

Anorexia

Malaise

Physical examination may reveal the following in patients with the disorder:

Fever: Especially in more severe cases

Dehydration

Lower abdominal tenderness

Rebound tenderness: Raises the possibility of colonic perforation and peritonitis

See Clinical Presentation for more detail.

Diagnosis

The diagnosis of C difficile colitis should be suspected in any patient with diarrhea who has received antibiotics within the previous 3 months, has been recently hospitalized, and/or has an occurrence of diarrhea within 48 hours or more after hospitalization.
In addition, C difficile can be a cause of diarrhea in community dwellers without previous hospitalization or antibiotic exposure.

Laboratory studies

Laboratory testing for evaluating patients with CDI includes the following:

Complete blood count: Leukocytosis may be present (the levels can be very high in severe infection)

Electrolyte levels, including serum creatinine: Dehydration, anasarca, and electrolyte imbalance may accompany severe disease

Albumin levels: Hypoalbuminemia may accompany severe disease

Serum lactate level: Lactate levels are generally elevated (≥5 mmol/L) in severe disease

Stool examination: Stool may be positive for blood in severe colitis, but grossly bloody stools are unusual; fecal leukocytes are present in about half of cases

Stool assays for C difficile, from the most to the least sensitive, include the following:

Stool culture: The most sensitive test (sensitivity, 90-100%; specificity, 84-100%), but the results are slow and may lead to a delay in the diagnosis if used alone

Glutamate dehydrogenase enzyme immunoassay (EIA): This is a very sensitive test (sensitivity, 85-100%; specificity, 87-98%); it detects the presence of glutamate dehydrogenase produced by C difficile

Real-time polymerase chain reaction (PCR) assay: This test is an alternative gold standard to stool culture (sensitivity, 86%; specificity, 97%
); it may be used to detect the C difficile gene toxin

Stool cytotoxin test: A positive test result is the demonstration of a cytopathic effect that is neutralized by a specific antiserum (sensitivity, 70-100%; specificity, 90-100%)

EIA for detecting toxins A and B: This test is used in most laboratories (moderate sensitivity, 79-80%; excellent specificity, 98%)

Latex agglutination technique: Another means of detecting glutamate dehydrogenase; however, the sensitivity of this test is poor (48-59%), although the specificity is 95-96%

Imaging studies and procedures

Abdominal computed tomography (CT) scanning is the imaging modality of choice for C difficile colitis when pseudomembranous colitis (see the image below), complications of CDI, or other intra-abdominal pathology is suspected.
In patients with sepsis due to suspected megacolon, abdominal radiography may be performed instead of CT scanning to establish the presence of megacolon in a timely manner.

Clostridioides (Clostridium) difficile colitis. Co

Clostridioides (Clostridium) difficile colitis. Computed tomography scan of pseudomembranous colitis.

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Endoscopy is less sensitive for diagnosing C difficile than are stool assays. Endoscopy may demonstrate the presence of raised, yellowish white, 2- to 10-mm plaques overlying an erythematous and edematous mucosa. These plaques are termed pseudomembranes. Endoscopic findings may be normal in patients with mild disease or may demonstrate nonspecific colitis in moderate cases.

See Workup for more detail.

Management

Treatment for CDI varies according to its severity. Interventions include the following:

Asymptomatic carriers: No treatment is necessary

Mild, antibiotic-associated diarrhea without fever, abdominal pain, or leukocytosis: Cessation of antibiotic(s) may be the only treatment necessary

Mild to moderate diarrhea or colitis: Metronidazole (oral or intravenous) or vancomycin (oral) for 10 days

Severe or complicated disease: Vancomycin is considered to produce faster symptom resolution and fewer treatment failures than metronidazole; in fulminant cases, combined therapy with intravenous metronidazole and oral (or per rectum) vancomycin may be considered

Relapse

Relapse occurs in 20-27% of patients. Once a patient has 1 relapse, the risk for a second relapse is 45%. Relapses should be treated as follows:

First relapse: The choice of antibiotic should be based on the severity of C difficile diarrhea/colitis

Subsequent relapses: For every relapse after the first, vancomycin (prolonged taper/pulsed regimen) or fidaxomicin with or without probiotics is recommended

Among various investigational therapies, fecal microbiota transplantation (fecal enemas or infusion of donor feces through a nasoduodenal tube) has been reported to repopulate the colonic flora and treat recurrent CDI.

See Treatment and Medication for more detail.

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