A 28-year-old woman with community-acquired pneumonia is started on azithromycin. On day 3 of therapy, she develops severe abdominal pain, diarrhea, and fever. Stool culture grows Clostridioides difficile. Which investigation is most appropriate to confirm the diagnosis of antibiotic-associated C. difficile colitis?

Explanation

## Diagnosis of C. difficile Infection (CDI) ### Gold Standard Investigation **Key Point:** Stool toxin assay (enzyme immunoassay for toxins A and B) or NAAT (nucleic acid amplification test targeting toxin genes) is the investigation of choice for confirming C. difficile colitis. ### Why Toxin Detection is Preferred **High-Yield:** The diagnosis of CDI requires BOTH: 1. Clinical symptoms (diarrhea, abdominal pain, fever) 2. Laboratory evidence of C. difficile toxins or toxigenic organism - **Toxin assay** detects pathogenic toxins (A and B) directly in stool - **NAAT** is highly sensitive and specific; detects toxin genes (tcdA, tcdB) in toxigenic strains - Both methods confirm that the organism present is actually pathogenic ### Why Other Options Are Incorrect | Investigation | Limitation | |---|---| | Stool culture (CCFA agar) | Grows C. difficile but does NOT distinguish toxigenic from non-toxigenic strains; colonization ≠ infection | | Colonoscopy with biopsy | Invasive; reserved for fulminant colitis or toxic megacolon; pseudomembranes are NOT required for diagnosis | | Serum procalcitonin | Non-specific marker of systemic inflammation; does not confirm CDI | **Clinical Pearl:** In macrolide-associated CDI, azithromycin disrupts normal colonic flora, allowing toxigenic C. difficile to proliferate. Diagnosis is microbiological, not clinical alone. **Warning:** Do NOT rely on stool culture alone — many patients carry non-toxigenic C. difficile without disease. Toxin or toxin gene detection is mandatory. [cite:Harrison 21e Ch 157]