Is stool testing for Clostridioides difficile (C. difficile) toxin appropriate following treatment for C. difficile colitis?

Routine Stool Testing for C. difficile Toxin Following Treatment is NOT Recommended

Routine testing for C. difficile toxin after treatment completion should not be performed, as more than 60% of successfully treated patients remain C. difficile positive despite clinical resolution. 1

Why Test of Cure is Inappropriate

High Rate of Persistent Colonization

• Over 60% of patients who respond successfully to treatment continue to asymptomatically shed C. difficile spores for up to 6 weeks after symptom resolution 1
• Laboratory testing cannot distinguish between asymptomatic colonization and active infection 1
• Asymptomatic carriage is common in healthcare facilities and does not require treatment 1

No Clinical Value

• There is no clinical value in repeat CDI testing to establish cure 1
• Testing asymptomatic patients after treatment is not recommended except for epidemiologic purposes 2
• The presence of toxin or toxigenic bacteria without diarrhea does not equate with disease 3

When Testing IS Appropriate After Treatment

Recurrent Symptoms Only

• Testing should only be performed if diarrhea recurs after initial symptom resolution 1
• A recurrence of symptoms following successful treatment and diarrhea cessation should be assessed by repeat testing 1
• Ideally, testing for recurrent CDI should include toxin detection, as persistence of toxigenic C. difficile occurs commonly after infection 1

Important Clinical Context

• In one study, 35% of CDI patients with recurrent diarrhea tested negative for toxin, highlighting that empiric treatment without confirmatory testing is discouraged 1
• Patients can have reduced health scores and altered bowel habits for months after CDI, which may represent post-infectious irritable bowel syndrome rather than recurrent infection 1
• Up to 35% of patients experience recurrent symptoms due to transient functional bowel disorder in the first two weeks following CDI resolution 1

Special Consideration: Post-FMT Testing

For patients treated with fecal microbiota transplantation (FMT), routine testing for C. difficile toxin after FMT is not recommended 1

• Testing is only appropriate to consider in cases of persistent CDI symptoms or suspected relapse 1
• Treatment failure/recurrence should be defined on a case-by-case basis 1

Common Pitfalls to Avoid

Do Not Repeat Test Within 7 Days

• The diagnostic yield of repeat testing within a 7-day period is approximately 2% 1
• Repeat testing should not be performed in the absence of clear changes to clinical presentation (change in character of diarrhea or new supporting clinical evidence) 1
• Use of highly sensitive testing strategies means single tests have very high negative predictive value (typically >99%) 1

Focus on Clinical Resolution

• Diagnosis of cure should be based on clinical criteria (resolution of diarrhea), not laboratory testing 1
• Symptoms of CDI resolve relatively promptly after successful treatment (within hours to 4-5 days on average) 1
• Treatment success has no uniformly agreed definition and should be decided on a case-by-case basis 1

Risk of False Positives

• Multiple repeat testing runs a high risk of generating false-positive results, particularly with tests of suboptimal specificity 1
• Testing should only be done on patients with diarrhea (≥3 unformed stools in 24 hours) 1