A 68-year-old woman presents to the emergency room with several days of frequent, nonbloody, watery stools. She recently completed a course of clindamycin 2 weeks ago for a tooth infection. Her medical history is notable for hypertension and hyperlipidemia for which she takes amlodipine and atorvastatin. She traveled recently and has no sick contacts. Her temperature is 37.0°C (98.6°F), blood pressure is 118/82 mmHg, pulse is 98/min, respirations are 14/min, and oxygen saturation is 98% on room air. On exam, her abdomen is soft, non-distended, and non-tender to palpation; however she has diffuse discomfort upon palpation of the abdomen with no rebound, rigidity, or guarding. Which of the following is most likely to confirm the diagnosis?
CT imaging of abdomen and pelvis
Rectal swab for selective anaerobic culture
Abdominal radiograph
Stool toxin assay
Stool toxin assay
This patient presenting with cramping abdominal pain and frequent watery diarrhea a few weeks after finishing a course of antibiotics most likely has Clostridioides difficile infection, for which the most appropriate confirmatory test is a stool toxin assay.

C. difficile infection should be suspected in patients with acute and clinically significant diarrhea with no obvious alternative explanation. It is associated with risk factors such as recent antibiotic use, hospitalization, and advanced age. Diagnosis is established via a positive enzyme immunoassay for C. difficile toxins and C. difficile glutamate dehydrogenase (GDH), or a positive nucleic acid amplification test (NAAT) for C. difficile toxins. The GDH enzyme immunoassay is highly sensitive for detecting C. difficile, but not specific for toxin-producing C. difficile, and thus the toxin enzyme immunoassay is submitted in conjunction. If the results of both are discordant, then NAAT is used to make the diagnosis. Treatment for C. difficile infection differs by disease severity and recurrence. Commonly used medications include fidaxomicin and oral vancomycin.

McDonald et al. review the guidelines for diagnosis and treatment of C. difficile and provide the algorithm for C. difficile testing as mentioned above. The authors also note that only liquid stool from patients with clinically significant and acute diarrhea should be submitted for testing. The authors recommend that formed stool from asymptomatic patients should not be tested because the presence of the C. difficile toxin gene does not distinguish between infection and asymptomatic carriage.

Incorrect Answers:
Answer A: Abdominal radiograph is an appropriate adjunctive diagnostic tool in patients with severe disease (e.g., severe abdominal pain and distension, fever, hypovolemia, lactic acidosis, marked leukocytosis) or fulminant colitis (marked by hypotension and ileus) to evaluate for toxic megacolon, bowel perforation, or other findings that warrant surgical intervention. In patients who are stable with low concern for severe disease or fulminant colitis, it would not be the preferred initial test for diagnosis nor would it be confirmatory.

Answer B: CT imaging of the abdomen and pelvis with oral and intravenous contrast is the preferred modality for detecting the presence of toxic megacolon, bowel perforation, or other findings that warrant surgical intervention in the setting of C. difficile colitis. Colonic dilatation of > 7 cm in diameter in the clinical setting of severe C. difficile infection is diagnostic. Other findings may include small bowel dilatation or scalloping of the bowel wall due to submucosal edema. While it would be reasonable to perform a CT scan in this patient, it would not confirm the diagnosis.

Answer C: Flexible sigmoidoscopy would be appropriate for cases in which an alternative diagnosis is suspected that requires direct visualization and/or biopsy of the bowel mucosa. It may also be helpful for patients with ileus or colitis in the absence of diarrhea as it allows for visualization of pseudomembranes on the inflamed mucosal surface, which are highly suggestive of C. difficile infection. In general, colonoscopy is a preferred and more accurate test.

Answer D: Rectal swab for selective anaerobic culture involves culture on a selective medium with toxin testing of isolated C. difficile. It is a highly sensitive test, but culture cannot distinguish toxin-producing strains from non-toxin-producing strains. A second test is required to detect toxin production by the cultured C. difficile strain (either enzyme immunoassay or nucleic acid amplification testing). Culture takes several days to finalize and as such, it is seldom used to establish a clinical diagnosis. It is most useful in patients with ileus and suspected C. difficile infection.

Bullet Summary:
The most appropriate confirmatory test for diagnosis of Clostridioides difficile infection is a stool toxin assay.