Would fecal calprotectin be elevated in Clostridioides difficile infection?

Yes, fecal calprotectin is typically elevated in C. difficile infection

Fecal calprotectin is elevated in most patients with active Clostridioides difficile infection (CDI), particularly in those with detectable toxins in stool and more severe disease. However, it is not specific for CDI and cannot distinguish infection from colonization or other causes of intestinal inflammation.

Key Evidence on Calprotectin in CDI

Elevation Patterns

• Patients with CDI demonstrate significantly higher fecal calprotectin levels compared to controls 1
• Median calprotectin in CDI patients: 218.0 μg/g vs. 111.5 μg/g in diarrheal controls 1
• Mean levels around 331.4 μg/g (range 21-932 μg/g) have been reported 2
• Calprotectin is particularly elevated when free toxins are detectable in stool (274.0 vs. 166.0 μg/g in toxin-positive vs. toxin-negative CDI, p=0.051) 1

Clinical Utility and Limitations

For distinguishing true infection from colonization:

• Patients requiring CDI treatment have median calprotectin of 410 μg/g 3
• Presumed colonization or self-limited CDI shows median of only 51 μg/g 3
• Calprotectin <100 μg/g was found in 33.5% of patients who did not need treatment 3

For severity assessment:

• Higher calprotectin correlates with hypervirulent ribotype 027 strain (p<0.0005) 2
• Correlates with elevated peripheral white blood cell count (p=0.0007) 2
• Optimal cutoff of 439 μg/g predicts severe CDI with 43.9% specificity and 54.1% PPV 4

For predicting recurrence:

• Optimal cutoff of 1052 μg/g provides 60.9% specificity and 16.9% PPV for recurrence 4

Critical Caveats

Lack of Specificity

The 2023 AGA guidelines explicitly warn that fecal calprotectin may be elevated due to non-intestinal sources of infection or inflammation 5. The 2017 IDSA guidelines note insufficient data to recommend calprotectin for establishing infectious diarrhea etiology 6.

In patients with suspected CDI and elevated biomarkers, stool testing for C. difficile and other enteric pathogens is essential to rule out other gastrointestinal infections 5, 7.

Not a Diagnostic Test

• Calprotectin cannot replace molecular testing or toxin assays for CDI diagnosis 8
• It performs poorly for diagnosis and prognosis prediction 8
• Its primary potential value is as a screening marker and for severity assessment 8

Practical Application

When you encounter elevated calprotectin in a patient with diarrhea:

• Do not assume CDI - test specifically for C. difficile toxins/genes
• Consider other causes: inflammatory bowel disease, other bacterial infections, NSAID use
• If CDI is confirmed, higher calprotectin (>400-1000 μg/g) suggests more severe disease requiring closer monitoring
• Very low calprotectin (<100 μg/g) in a patient with positive C. difficile testing may indicate colonization rather than true infection 3

The bottom line: Calprotectin is elevated in CDI but is not specific enough to diagnose it or distinguish it from other inflammatory conditions affecting the gut.