How to Check for C. difficile Infection
Test patients who have ≥3 unformed stools in 24 hours using either a NAAT alone OR a multistep algorithm (GDH plus toxin; GDH plus toxin arbitrated by NAAT; or NAAT plus toxin) depending on whether your institution has strict stool submission criteria. 1
Who Should Be Tested
Only test patients meeting ALL of the following criteria:
- ≥3 unformed stools in 24 hours that are unexplained and new-onset 1
- Not currently taking laxatives 1
- Recent antibiotic exposure or healthcare facility contact increases suspicion 2
Critical pitfall: Do NOT test asymptomatic patients, formed stools, or patients simply to confirm cure after treatment 1. Do NOT test infants ≤12 months old routinely due to high asymptomatic colonization rates 1.
Testing Algorithm: Two Pathways Based on Institutional Criteria
Pathway 1: If Your Institution Has Strict Stool Submission Criteria
(Meaning: lab only accepts specimens from patients meeting the ≥3 unformed stools/24h criteria)
Use NAAT alone OR a multistep algorithm 1:
- NAAT alone offers 93-95% sensitivity 1, 3
- Multistep options:
- GDH + toxin EIA
- GDH + toxin EIA, with NAAT arbitration if discordant
- NAAT + toxin EIA
Why this matters: When you pre-screen patients clinically, NAAT's high sensitivity (>95%) becomes advantageous with acceptable positive predictive value 1.
Pathway 2: If Your Institution Lacks Strict Submission Criteria
(Meaning: any stool can be submitted without clinical vetting)
Must use a multistep algorithm with toxin detection rather than NAAT alone 1:
- Start with GDH (screening sensitivity ~91.6%) 4
- Follow positive GDH with toxin A/B EIA
- Use NAAT to arbitrate discordant results (GDH+/toxin-)
Rationale: NAAT alone in unscreened populations detects colonization (not just infection), leading to overdiagnosis, unnecessary treatment, and increased antimicrobial resistance 3. The multistep approach increases positive predictive value by requiring toxin presence 1.
Critical Testing Principles
Do NOT repeat testing within 7 days of the same diarrheal episode—diagnostic yield is only ~2% and risks false positives 1. The exception: if clinical symptoms significantly worsen or change character, consider repeat testing 1.
Toxin EIA sensitivity varies widely (53-73%) 1, 3, so laboratories should select assays in the upper sensitivity range if using toxin-based methods 1.
Special Populations
- Children 1-2 years: Only test if prolonged diarrhea with risk factors 2
- Recurrent symptoms after successful treatment: Retest is appropriate as this represents new episode, ideally including toxin detection 1
The Testing Nuance
The 2018 IDSA/SHEA guidelines [1-1 acknowledge a fundamental tension: NAAT is most sensitive but may detect asymptomatic carriers; toxin EIA is more specific for active disease but misses cases. The solution is context-dependent testing—strict clinical criteria allow NAAT alone, while broad testing requires multistep algorithms to balance sensitivity and specificity 1.
Bottom line: The testing method depends entirely on whether your institution enforces the ≥3 unformed stools criterion before specimen submission. Know your lab's protocol and advocate for appropriate test utilization to avoid both missed diagnoses and overtreatment.