What is the recommended treatment for a 59‑year‑old man with a history of lymphoma who presents with a one‑week history of acute diarrhea, a positive Clostridioides difficile toxin gene nucleic acid amplification test, and markedly elevated fecal calprotectin?

Treatment of Clostridioides difficile Infection in a Cancer Patient

This patient requires oral vancomycin 125 mg four times daily for 10 days as first-line therapy, with immediate discontinuation of any ongoing antibiotics and aggressive supportive care including IV hydration and electrolyte repletion. 1

Rationale for Vancomycin Over Metronidazole

• Metronidazole should be avoided in this patient because current guidelines recommend limiting metronidazole only to initial episodes of mild-moderate CDI in settings where vancomycin or fidaxomicin access is limited 1
• The markedly elevated fecal calprotectin of 1590 μg/g indicates severe intestinal inflammation and correlates with more severe disease, supporting the use of vancomycin as first-line therapy 2, 3
• In cancer patients with lymphoma, the immunocompromised state and history of malignancy automatically classify this as a complicated case requiring more aggressive therapy than metronidazole 1
• Repeated or prolonged courses of metronidazole carry risk of cumulative and potentially irreversible neurotoxicity and should be avoided 1

Specific Treatment Regimen

• Oral vancomycin 125 mg four times daily for 10 days is the recommended first-line therapy for this patient 1
• Fidaxomicin 200 mg twice daily for 10 days is an alternative option with similar efficacy, though vancomycin remains standard 1, 4
• If oral administration is not possible due to ileus or severe disease, vancomycin 500 mg via nasogastric tube or rectal enema should be considered 1

Critical Immediate Actions

• Discontinue all non-essential antibiotics immediately, as continued antibiotic use significantly increases risk of CDI recurrence 1
• Initiate aggressive IV fluid resuscitation to address dehydration indicated by the week-long diarrhea 1
• Obtain complete blood count to assess for neutropenia, which would further complicate management 1
• Check comprehensive metabolic panel including electrolytes, creatinine, and renal function 1

Significance of Elevated Fecal Calprotectin

• The fecal calprotectin level of 1590 μg/g is markedly elevated (normal <50 μg/g) and indicates severe intestinal inflammation 5, 2
• Higher calprotectin levels correlate with presence of free toxin in stool and more severe disease, supporting aggressive initial therapy 3, 6
• Calprotectin levels can be monitored at one week to assess treatment response, with persistently elevated levels (>285 μg/g) indicating treatment failure 5
• Elevated calprotectin in CDI patients, particularly those with detectable toxin, suggests correlation between intestinal inflammation severity and clinical outcomes 3

Special Considerations in Lymphoma Patients

• Cancer patients, particularly those with lymphoma, are at higher risk for severe CDI due to immunosuppression and frequent healthcare exposures 1
• A two-step microbiological approach is recommended: enzyme immunoassays detecting glutamate dehydrogenase followed by nucleic acid amplification tests for toxin genes 1
• In immunocompromised patients with CDI, empirical therapy should be considered while awaiting test results if there is strong clinical suspicion for severe disease 1

Monitoring and Follow-up

• Monitor stool frequency, consistency, and volume daily during treatment 1
• Reassess electrolytes and renal function daily until normalized 1
• Repeat fecal calprotectin at 7 days can help assess treatment response, with levels >285 μg/g suggesting persistent disease 5
• Watch for signs of complicated CDI including fever, leukocytosis >15,000, creatinine >1.5x baseline, or hypotension requiring vasopressors 1

Common Pitfalls to Avoid

• Do not use metronidazole as first-line therapy in this immunocompromised patient with severe inflammation 1
• Do not continue loperamide or other antidiarrheal agents, as they increase risk of toxic megacolon in CDI 1
• Do not delay treatment while waiting for additional test results if clinical suspicion is high 1
• Do not discontinue proton pump inhibitors reflexively without considering the indication, though stewardship to discontinue unneeded PPIs is warranted 1

Dietary and Supportive Measures

• Eliminate lactose-containing products, alcohol, and high-osmolar dietary supplements 1
• Encourage consumption of 8-10 large glasses of clear liquids daily (electrolyte solutions, broth) 1
• Recommend small, frequent meals following the BRAT diet (bananas, rice, applesauce, toast, plain pasta) 1

Recurrence Risk Management

• This patient is at increased risk for recurrence given the cancer history and immunosuppression 1
• If recurrence occurs after initial treatment, consider extended vancomycin taper or fidaxomicin for subsequent episodes 1
• Fecal microbiota transplantation may be considered for multiple recurrences, though data in severely immunocompromised patients is limited 1