How do you diagnose C. diff infection in a patient with diarrhea undergoing chemoradiation with cisplatin for p16+ squamous cell carcinoma of the tongue?

Diagnosing C. difficile Infection in Cancer Patients Undergoing Chemoradiation

For patients undergoing chemoradiation with cisplatin for p16+ squamous cell carcinoma of the tongue with diarrhea, testing for C. difficile should be performed using a two-step approach with enzyme immunoassays (EIAs) for glutamate dehydrogenase and toxins A/B, or nucleic acid amplification tests. 1

Risk Factors and Context

• Cancer patients receiving chemoradiation are at increased risk for C. difficile infection due to disruption of gastrointestinal microflora from both chemotherapy and antibiotics 1
• In cancer patients with diarrhea, C. difficile overgrowth occurs in 7-50% of cases following antibiotic administration 1
• Patients receiving cisplatin-based regimens for head and neck cancers are particularly susceptible to treatment-associated diarrhea 2
• While chemotherapy toxicity is the most common cause of diarrhea in cancer patients, infectious causes must always be ruled out before symptomatic management 1

Diagnostic Algorithm

Step 1: Initial Assessment

• Evaluate diarrhea severity, duration, and associated symptoms (fever, abdominal pain, blood in stool) 1
• Assess for risk factors: recent antibiotic use, hospitalization, immunosuppression from cancer treatment 1
• Check for warning signs of complicated diarrhea: fever, neutropenia, dehydration, severe cramping 1

Step 2: Laboratory Testing

• Primary C. difficile Testing:

  • Use a two-step approach recommended by most guidelines 1:
    1. EIA for glutamate dehydrogenase (GDH) detection
    2. EIA for toxins A and B detection
  • Alternatively, nucleic acid amplification tests (NAATs) can be used 1

• Additional Testing:

  • Complete blood count to assess for neutropenia and leukocytosis 1
  • Electrolytes, creatinine, and BUN to evaluate hydration status 1
  • Blood cultures if fever is present (minimum two sets including from any indwelling catheters) 1

Step 3: Extended Workup (if initial tests negative or symptoms persist)

• Test for other enteric pathogens: Salmonella, Shigella, Campylobacter, Yersinia 1
• Consider viral causes: adenovirus, astrovirus, CMV, norovirus, rotavirus 1
• Evaluate for parasitic infections 1
• Consider lactose breath test for chemotherapy-associated lactose intolerance 1

Special Considerations

• Neutropenic patients may not develop typical pseudomembranes on endoscopy as their formation requires neutrophils 1
• In patients with persistent symptoms despite negative initial testing, repeat C. difficile testing may be warranted 1
• Colonoscopy is generally not recommended in neutropenic patients due to increased risk of perforation 1
• For patients with p16+ squamous cell carcinoma specifically, the risk of treatment-related complications including diarrhea may be significant due to intensive chemoradiation protocols 3, 4

Management Implications

• Confirmation of C. difficile infection will guide appropriate antimicrobial therapy 1
• If C. difficile is ruled out, treatment for non-infectious diarrhea can be initiated with loperamide 1
• For loperamide-refractory cases, octreotide may be considered after infectious causes are excluded 1
• Patients with complicated diarrhea may require IV fluids, antibiotics, and possibly hospitalization 1

By following this systematic approach to diagnosing C. difficile infection in cancer patients undergoing chemoradiation, clinicians can ensure appropriate management and prevent potentially life-threatening complications.