When should C-diff (Clostridioides difficile) testing be repeated in inpatients?

When to Repeat C. difficile Testing in Inpatients

Do not repeat C. difficile testing within 7 days during the same diarrheal episode—the diagnostic yield is only 2% and repeat testing is strongly discouraged. 1, 2

Core Testing Principles

Avoid routine repeat testing because:

• The proportion of patients transitioning from negative to positive C. difficile results within a 7-day window is only 3% (95% CI, 0.023 to 0.038) 2
• Highly sensitive testing strategies (two-step algorithms or stand-alone NAATs) have negative predictive values >99%, making repeat testing unnecessary 1
• More than 60% of successfully treated patients remain C. difficile positive even after clinical cure, so "test of cure" is not recommended 1, 2

When Repeat Testing MAY Be Considered

For suspected recurrence after successful treatment:

• Test only when diarrhea recurs following documented symptom resolution and completion of therapy 1
• Recurrent CDI is defined as clinically significant diarrhea with a confirmatory positive test within 8 weeks of completing antibiotics 1
• Ideally include toxin detection for recurrence testing, as 35% of patients with recurrent diarrhea after CDI treatment test negative for toxin 1

For patients with high clinical suspicion and worsening symptoms:

• If symptoms worsen despite a negative initial test in a patient with very high pretest probability, repeat testing may be considered—but this does not equate to routine retesting 1
• In epidemic settings where CDI acquisition is more frequent, there may be slightly more value to repeat testing 1

Special Population: IBD Patients

Inflammatory bowel disease patients are an exception where repeated testing may be necessary:

• Symptoms related to CDI overlap with IBD flares, creating diagnostic challenges when assessing treatment failure 1
• In this specific setting, repeated testing in symptomatic patients may be necessary to distinguish CDI from disease flare 1
• Treatment response in non-IBD patients should be based only on clinical assessment, but IBD patients require a different approach 1

What to Do Instead of Repeat Testing

When diarrhea persists beyond expected timeframe:

• Consider alternative diagnoses rather than reflexively retesting for C. difficile 2
• Evaluate for post-infectious irritable bowel syndrome, which can occur following CDI 1, 2
• Look for atypical symptoms (diarrhea alternating with constipation, no response to vancomycin/fidaxomicin) suggesting alternative diagnosis 1, 2
• Assess for complications of severe or fulminant CDI requiring escalation of therapy rather than repeat testing 2

For treatment failure:

• Empiric treatment without confirmatory testing of suspected recurrence is discouraged 1
• Clinical response may require 3-5 days after starting therapy, so allow adequate time before concluding treatment failure 1
• Therapy escalation can be considered sooner based on disease severity without repeat testing 1

Common Pitfalls to Avoid

• Never test asymptomatic patients, even with a history of C. difficile—this only detects colonization, not infection 1, 2
• Never perform "test of cure" after completing CDI treatment, as persistent positivity is common and clinically meaningless 1, 2
• Do not submit specimens from patients receiving laxatives, as this increases false-positive rates 1
• Only test patients with ≥3 unformed stools in 24 hours with new-onset diarrhea and appropriate risk factors 1