Should You Be Tested for C. difficile?
You should be tested for C. difficile infection if you have unexplained, new-onset diarrhea with ≥3 unformed stools in 24 hours, particularly if you have recent antibiotic exposure, healthcare contact, or are over 50 years old. 1
Who Should Be Tested
The 2018 IDSA/SHEA guidelines clearly define the target population for testing 1:
- Adults with ≥3 unformed stools in 24 hours that are unexplained and new-onset
- Recent antibiotic use (within past 3 months) significantly increases suspicion
- Recent hospitalization or healthcare facility exposure
- Age ≥50 years is a traditional risk factor
- Underlying conditions such as inflammatory bowel disease or immunocompromising conditions
Importantly, about one-third of community-acquired CDI cases occur without recent antibiotic exposure or hospitalization 2, so don't rule out testing based solely on absence of these factors if diarrhea is severe or persistent.
Who Should NOT Be Tested
Do not test in the following situations 1:
- Asymptomatic patients (except for epidemiological studies)
- Infants ≤12 months of age - they have high rates of asymptomatic colonization and testing is never routinely recommended
- Children 1-2 years old - only test if other infectious and non-infectious causes have been excluded
- Patients on laxatives - institutional protocols should exclude these patients from testing
- Formed stools - only unformed/liquid stools should be tested
- Repeat testing within 7 days during the same diarrheal episode - this is strongly discouraged as the diagnostic yield is only ~2% 1
Testing Approach
The guidelines recommend specific testing algorithms rather than single tests 1:
When institutional criteria for stool submission are established (screening for appropriate symptoms before testing):
- Use NAAT alone OR
- Use a multistep algorithm (GDH plus toxin; GDH plus toxin arbitrated by NAAT; or NAAT plus toxin)
When there are no pre-agreed institutional criteria (all submitted specimens tested):
- Use NAAT plus toxin rather than NAAT alone to improve positive predictive value
The rationale: NAAT is highly sensitive but can detect asymptomatic colonization. Adding toxin testing increases specificity for clinically significant infection 1. However, toxin EIA alone has poor sensitivity (<30% in some studies) and should never be used as a standalone test 3.
Special Considerations for Children
- Children ≥2 years: Test if they have prolonged or worsening diarrhea with risk factors (IBD, immunocompromise) or relevant exposures (healthcare contact, recent antibiotics) 1
When to Retest
Do retest if 1:
- Symptoms recur after successful treatment and resolution of diarrhea (this represents potential recurrence, not the same episode)
- High clinical suspicion persists with worsening symptoms despite initial negative test
Do not retest within 7 days during the same diarrheal episode - the yield is extremely low and risks false positives 1
Common Pitfalls to Avoid
- Testing patients without diarrhea - this only detects colonization, not infection
- Testing too frequently - repeat testing within a week is wasteful and misleading
- Ignoring clinical context - a positive PCR/NAAT in someone without appropriate symptoms may represent colonization rather than infection
- Testing children under 1 year - nearly always inappropriate due to high colonization rates
- Using toxin EIA alone - insufficient sensitivity will miss true cases 3
The key is diagnostic stewardship: only test patients who meet clinical criteria for suspected CDI, as indiscriminate testing leads to false positives, unnecessary treatment, and misuse of resources 4.