Will C. diff Test Positive After Recent Infection?
No, a positive C. difficile test after recent infection does not necessarily indicate active toxin production or new infection—it may simply reflect persistent colonization with toxigenic strains, which occurs in over 60% of successfully treated patients. 1
Key Principle: Distinguish Between Colonization and Active Infection
The critical issue is understanding what different tests actually detect:
- NAATs (PCR tests) detect toxin-encoding genes (tcdB or tcdC), not actual toxins themselves, meaning they cannot distinguish between active infection and asymptomatic colonization 2
- Approximately 7% of asymptomatic hospitalized patients are colonized with toxigenic C. difficile, carrying the organism with toxin genes but not actively infected 2
- More than 60% of patients remain C. difficile positive even after successful treatment, making post-treatment testing clinically meaningless 1
When to Retest After Recent Infection
Do not perform repeat testing within 7 days during the same episode of diarrhea, and do not test stool from asymptomatic patients (strong recommendation, moderate quality evidence) 1
Appropriate scenarios for retesting:
- Recurrence of symptoms after successful treatment and diarrhea cessation should be assessed by repeat testing, ideally including toxin detection since persistence of toxigenic C. difficile commonly occurs after infection 1
- In one study, 35% of CDI patients with recurrent diarrhea tested negative for toxin, emphasizing that empiric treatment without confirmatory testing is discouraged 1
- Patients with high clinical suspicion whose symptoms worsen may warrant repeat testing, but this does not equate to routine retesting 1
Clinical Implications for Interpretation
If testing is performed despite guidelines:
- Toxin-positive patients (by EIA) are more likely to have severe/complicated forms and recurrences compared to toxin-negative/PCR-positive patients (adjusted OR 2.11 for severe disease; adjusted OR 3.79 for recurrence) 3
- Patients who are NAAT-positive but toxin-negative may represent colonization rather than active infection, particularly if they lack typical CDI symptoms (≥3 unformed stools in 24 hours) 2, 4
- The diagnostic yield of repeat testing within 7 days is approximately 2% with either toxin EIA or NAAT 1
Common Pitfalls to Avoid
- Never test for cure—there is no clinical value in repeat CDI testing to establish cure, as most patients remain positive after successful treatment 1
- Do not test asymptomatic patients—testing formed stool or asymptomatic individuals results in false positives and unnecessary treatment 2, 4
- Recognize that positive NAAT does not automatically confirm CDI—clinical correlation is essential, and alternative diagnoses should be considered in patients without typical symptoms 2
- Patients can have altered bowel habits for prolonged periods after CDI, with reduced health scores for months, which should not trigger reflexive retesting 1
Recommended Approach for Suspected Recurrence
Use a two-step algorithm when testing for recurrence: GDH screening followed by toxin detection (either toxin EIA or NAAT), rather than NAAT alone, to balance sensitivity with clinical specificity 2, 4