Clostridioides (formerly Clostridium) difficile–Induced Diarrhea

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

C. difficile–induced colitis may also follow 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. 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, which rarely develops, is somewhat more likely after use of antimotility medications. Limited tissue dissemination occurs very rarely, as do sepsis and acute abdomen. Reactive arthritis rarely has occurred after C. difficile–induced diarrhea.

Symptoms of C. difficile–induced diarrhea 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.

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.

C. difficile–induced diarrhea should be suspected in any patient who develops diarrhea within 2 months of antibiotic use or 72 hours of hospital admission.

Glutamate dehydrogenase (GDH) antigen is produced by all C. difficile strains. Enzyme-linked immunosorbent assay (ELISA) testing for the antigen is sensitive and can be done very quickly. However, a positive test indicates only presence of the organism not whether it is toxigenic (1 Diagnosis reference Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ).

Toxin assays using ELISA also can be done quickly and are very specific for active disease but are not particularly sensitive, so there is a significant number of false-negative results.

A nucleic acid amplification test Nucleic acid amplification Nucleic acid–based methods detect organism-specific DNA or RNA sequences extracted from the microorganism. Sequences may or may not be amplified in vitro. Nucleic acid–based (molecular) identification... read more (NAAT) using PCR to test for the toxin gene is very sensitive for toxigenic strains but cannot tell whether they 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 possibility of a carrier state, testing is usually done only on symptomatic patients (ie, those with multiple liquid stools). Because of the test characteristics, 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 Diagnosis reference Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ).

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 x-rays, CT, or both are usually done if fulminant colitis, perforation, or megacolon is suspected.

Oral vancomycin or oral fidaxomicin is recommended by the American College of Gastroenterology (1 Treatment references Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ) for the treatment of a primary episode of nonsevere C. difficile–induced diarrhea.

Fidaxomicin 200 mg orally every 12 hours for 10 days is recommended by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) as first-line therapy for C. difficile infection (2 Treatment references Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ). Fidaxomicin decreases the risk of recurrence more than vancomycin. Vancomycin 125 mg orally 4 times a day for 10 days is an alternative (2 Treatment references Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ).

Metronidazole is no longer recommended as first-line therapy for C. difficile–induced diarrhea. 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 and 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 (1 Treatment references Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ).

If possibly causative antibiotics are being used, they 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, Saccharomyces boulardii yeast, and probiotics have not been proved to be beneficial but are frequently added.

Nitazoxanide appears to be comparable to oral vancomycin but is not commonly used in the United States.

A few patients require total colectomy for cure.

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