What is the next step for a patient receiving chemotherapy who develops fever, is started on antibiotics, and later presents with watery diarrhea without mucus or blood?

PCR for C. diff Toxins is the Appropriate Next Step for Chemotherapy Patient with Watery Diarrhea After Antibiotics

The appropriate next step for a patient receiving chemotherapy who presents with fever, is started on antibiotics, and later develops watery diarrhea without mucus or blood is PCR for C. difficile toxins.

Rationale for C. difficile Testing

Patients receiving chemotherapy who develop diarrhea after antibiotic therapy are at high risk for C. difficile infection (CDI), which is the most common readily identifiable cause of infectious diarrhea in this setting 1. Several factors support this approach:

• Antibiotics disrupt normal gut flora, allowing C. difficile to proliferate
• Chemotherapy causes immunosuppression, increasing infection risk
• Watery diarrhea without blood or mucus is the classic presentation of CDI
• The sequence of events (chemotherapy → fever → antibiotics → diarrhea) strongly suggests antibiotic-associated diarrhea

Diagnostic Testing Options

PCR for C. difficile Toxins (Recommended)

• Highest sensitivity (>90%) and rapid turnaround time
• Detects genes encoding toxins A and B
• Allows for prompt initiation of appropriate therapy
• Current standard of care for initial testing 2

Cytotoxic C. difficile Toxins

• Lower sensitivity (60-90%) compared to PCR 1
• Longer turnaround time (24-48 hours)
• May miss cases that PCR would detect

Stool Culture

• Low yield in this clinical scenario
• Time-consuming (requires 48-72 hours)
• Not specific for toxigenic strains
• Studies show that for each positive C. difficile assay in PBPC transplant patients, 41 stool samples need to be analyzed 3

Management Algorithm

1. Obtain PCR for C. difficile toxins

2. While awaiting results:

   • Implement dietary modifications (eliminate lactose-containing products, alcohol, high-osmolar supplements)
   • Ensure adequate hydration (8-10 large glasses of clear liquids daily)
   • Consider holding chemotherapy until symptoms resolve 1

3. If PCR is positive:

   • For mild-moderate CDI: Oral vancomycin 125 mg four times daily for 10 days 4
   • For severe CDI: Oral vancomycin 125 mg four times daily plus IV metronidazole
   • Consider fidaxomicin for recurrent cases 5

4. If PCR is negative:

   • Consider other causes:
     • Chemotherapy-induced diarrhea
     • Other infectious causes (viral, parasitic)
     • SIBO (small intestinal bacterial overgrowth)

Important Considerations

• C. difficile can present atypically in immunocompromised patients, sometimes without diarrhea (ileus, toxic megacolon) 6
• Severe leukocytosis (≥30,000 cells/mm³) should raise suspicion for CDI even without typical symptoms 1
• Multiple C. difficile tests may be needed as sensitivity of a single test is not 100%
• While empiric treatment for C. difficile is common in some centers, it should be based on testing results when possible 3

Other Potential Causes to Consider

Although C. difficile is most likely, other causes to consider if PCR is negative include:

• Direct chemotherapy-induced mucosal damage
• Other infectious agents (rare but reported in immunocompromised patients):
  • Giardia lamblia 7
  • Cryptosporidium
  • Viral pathogens

PCR testing for C. difficile toxins provides the best balance of sensitivity, specificity, and rapid turnaround time, allowing for prompt initiation of appropriate therapy in this high-risk patient.