What diagnostic tests and treatment can a patient with Clostridioides difficile (C-diff) infection expect upon admission?

Expected Orders Upon Admission for C. difficile Infection

Upon admission with suspected C. difficile infection, expect immediate stool testing using a two-step diagnostic algorithm, contact isolation precautions, discontinuation of non-essential antibiotics, and empiric oral vancomycin 125 mg four times daily if severe disease is suspected. 1, 2

Diagnostic Testing Orders

Stool specimen collection and testing should be ordered immediately for patients with ≥3 unformed stools in 24 hours. 1, 2 The recommended approach is a two-step algorithm: either GDH screening followed by toxin testing, or NAAT (PCR) followed by toxin confirmation, which balances sensitivity (91%) and specificity (98%) while avoiding false positives from asymptomatic colonization. 3, 2

• Single toxin EIA alone is not recommended due to insufficient sensitivity (70-80%). 3, 2
• Testing should only be performed on unformed stool samples—testing formed stool leads to false positives and unnecessary treatment. 3, 4
• In patients with suspected severe CDI complicated by ileus who cannot produce stool, perirectal swabs can be used with PCR testing (95.7% sensitivity, 100% specificity). 4
• Do not order repeat testing if initial test is negative unless clinical suspicion remains extremely high—repeat stool testing has minimal added value. 5

Laboratory Studies

Complete blood count with differential should be ordered to assess for leukocytosis, which is a marker of severe disease. 6 White blood cell counts can reach leukemoid ranges (≥15,000/mm³ defines severe disease). 7, 6

Comprehensive metabolic panel to evaluate for:

• Hypoalbuminemia (often overlooked marker of severe disease) 6
• Electrolyte disturbances including hypokalemia and hypomagnesemia 2
• Acute kidney injury from dehydration 2

Infection Control Orders

Contact isolation precautions must be implemented immediately upon suspicion, before test results return. 2

Soap and water handwashing orders for all healthcare workers—alcohol-based sanitizers do not inactivate C. difficile spores, and mechanical removal through friction and running water is the only effective method. 1

Medication Orders

Discontinue causative antibiotics if clinically feasible, as continued antibiotic use significantly increases recurrence risk. 1, 2

Treatment Based on Severity:

For mild-to-moderate CDI:

• Oral metronidazole 500 mg three times daily for 10 days 3, 2
• OR oral vancomycin 125 mg four times daily for 10 days (preferred if intolerant to metronidazole) 3

For severe CDI (≥10 unformed stools/day OR WBC ≥15,000/mm³):

• Oral vancomycin 125 mg four times daily for 10-14 days (clinical success rate ~81%) 3, 2, 7

For severe-complicated CDI (hypotension, ileus, megacolon):

• Oral vancomycin 125-500 mg four times daily 3
• PLUS vancomycin per rectum 500 mg in 500 mL saline as enema four times daily 3
• AND/OR metronidazole 500 mg IV every 8 hours 3

Empiric therapy should be started immediately if high suspicion of severe CDI exists, even before test results. 3, 2

Contraindicated Orders

Absolutely do NOT order antiperistaltic agents (loperamide, diphenoxylate) as they worsen disease severity, mask symptoms, and precipitate toxic megacolon by trapping toxins against the colonic wall. 1

• If symptomatic management is needed, opioids or octreotide can be used as alternatives. 1

Additional Considerations

Proton pump inhibitors should be discontinued if possible, as they increase recurrence risk. 3

Imaging orders (CT abdomen/pelvis) may be needed if severe disease is suspected with ileus, toxic megacolon, or peritoneal signs. 6

Endoscopy is reserved for cases with extremely high clinical suspicion but persistently negative stool tests, or when immediate diagnosis is critical—it has only 51-55% sensitivity for CDAD but can visualize pseudomembranes. 8, 9, 6

Do NOT order "test of cure" after treatment completion, as patients may shed spores for up to 6 weeks after successful treatment. 3, 2

Common Pitfalls to Avoid

• Testing asymptomatic patients detects colonization rather than infection—only test symptomatic patients with diarrhea. 2, 4, 8
• Ordering multiple repeat tests when initial testing is negative adds minimal value unless clinical suspicion remains extremely high. 5
• Continuing slow-release oral medications during active diarrhea—rapid transit time prevents adequate absorption. 2
• Failing to monitor electrolytes in severe disease—hypomagnesemia and hypokalemia worsen outcomes and contribute to toxic megacolon. 2