Clostridioides difficile Infection

Antibiotic-induced changes in gastrointestinal flora are the dominant predisposing factors. Although most antibiotics have been implicated, the following pose the highest risk:

• Cephalosporins (particularly third-generation)

• Penicillins (particularly ampicillin and amoxicillin)

• Clindamycin

• Fluoroquinolones

CDI may also occur after use of certain antineoplastic medications.

The organism secretes both an enterotoxin and a cytotoxin, typically referred to as toxins A and B. However, not all strains of C. difficile produce toxins, and some people are asymptomatic carriers of toxin-producing strains. This carriage is particularly common among infants (1). The main effect of the toxin is on the colon, which secretes fluid and develops characteristic pseudomembranes—discrete yellow-white plaques that are easily dislodged. Plaques may coalesce in severe cases.

Toxic megacolon, although rare, is somewhat more likely after use of antimotility medications. Limited tissue dissemination occurs very rarely, as do sepsis and acute abdomen.

Reactive arthritis has rarely occurred after CDI.

Symptoms typically begin 5 to 10 days after starting antibiotics but may occur on the first day or up to 2 months later.

Diarrhea may be mild and semiformed, frequent and watery, or sometimes bloody. Cramping or pain is common, but nausea and vomiting are rare. The abdomen may be slightly tender. Fever and leukocytosis may be present.

Patients with fulminant colitis, which is characterized by severe acute inflammation of the colon and systemic toxicity, have more pain and appear very ill, with tachycardia and abdominal distention and tenderness. If colonic perforation occurs, peritoneal signs are present.

• Stool assay for glutamate dehydrogenase (GDH) antigen

• Stool assay for C. difficile toxin

• Nucleic acid amplification test for the toxin gene

• Sometimes sigmoidoscopy

C. difficile infection should be suspected in any patient who develops new and persistent diarrhea within 2 months of antibiotic use or 72 hours of hospital admission in the absence of an alternate etiology, such as laxative use or enteral nutrition delivered through a feeding tube.

Glutamate dehydrogenase (GDH) antigen is produced by all C. difficile strains. Enzyme-linked immunosorbent assay (ELISA) testing for the antigen in stool is sensitive and can be done very quickly. However, a positive test indicates only presence of the organism not whether it is toxigenic (1).

Toxin assays using ELISA also can be done quickly. The assay is specific for active disease but is not particularly sensitive, so false-negative results occur.

A nucleic acid amplification test (NAAT) using polymerase chain reaction (PCR) to test for the toxin gene is very sensitive for the presence of toxigenic strains but does not detect whether the organisms are actively producing toxin. This test often remains positive after successful treatment, so it can be difficult to interpret in patients with known previous disease.

Because of the high rates of colonization, testing should be done only on symptomatic patients (ie, those with multiple liquid stools), and test results need to be interpreted in the appropriate clinical context. Several or all of these tests are usually done, either sequentially or at once. One strategy is to first do GDH and toxin assays. If these are concordant (ie, both positive or both negative), then disease is considered confirmed or excluded. Discordant test results (ie, one positive, one negative) are resolved based on results of NAAT testing (1).

A single stool sample is usually adequate. If the first sample is negative, repeat samples should not be submitted for a minimum of 7 days unless there is a clinical change and the suspicion is high. Fecal leukocytes are often present but not specific.

Sigmoidoscopy, which can confirm the presence of pseudomembranes, should be done if patients have ileus or if toxin assays are nondiagnostic.

Abdominal radiographs, CT scans, or both are performed if fulminant colitis, perforation, or megacolon is suspected.

• Oral vancomycin or oral fidaxomicin

Oral vancomycin or oral fidaxomicin for 10 days is recommended by the American College of Gastroenterology (Oral vancomycin or oral fidaxomicin for 10 days is recommended by the American College of Gastroenterology (1) for the treatment of a primary episode of nonsevere C. difficile–induced diarrhea.

Fidaxomicin is preferentially recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) as first-line therapy for Fidaxomicin is preferentially recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) as first-line therapy forC. difficile infection (2). Fidaxomicin is more effective than vancomycin in decreasing the risk of recurrence, but vancomycin remains an alternative. Nitazoxanide seems to be comparable to oral remains an alternative. Nitazoxanide seems to be comparable to oralvancomycin but is not commonly used in the United States.

Metronidazole is not recommended as first-line therapy for Metronidazole is not recommended as first-line therapy forC. difficile–induced diarrhea in adults. However, oral metronidazole can be used if vancomycin or fidaxomicin is not available.

Vancomycin 500 mg orally or by nasogastric tube 4 times a day along with metronidazole 500 mg IV every 8 hours are recommended by the ISDA/SHEA for fulminant disease without ileus.Vancomycin 500 mg orally or by nasogastric tube 4 times a day along with metronidazole 500 mg IV every 8 hours are recommended by the ISDA/SHEA for fulminant disease without ileus.

If ileus is present, a retention enema can be given as a dosage of vancomycin 500 mg in 10 mL saline per rectum 4 times a day (If ileus is present, a retention enema can be given as a dosage of vancomycin 500 mg in 10 mL saline per rectum 4 times a day (1).

Antibiotics that are most likely to cause C. difficile–induced diarrhea should be stopped as soon as possible, or patients should be switched to an antibiotic regimen less likely to cause C. difficile–induced diarrhea.

Cholestyramine resin, Cholestyramine resin,Saccharomyces boulardiiSaccharomyces boulardii yeast, and probiotics have not been proved to be beneficial but are frequently added.

A few patients require total colectomy for treatment of fulminant disease.