Procalcitonin Elevation in Clostridium difficile Infection
Yes, procalcitonin (PCT) levels do increase in Clostridium difficile infection, with median levels significantly elevated compared to non-infected patients, and higher PCT levels correlate with disease severity. 1, 2
Magnitude of PCT Elevation
Median PCT levels in CDI patients reach 0.69 ng/mL compared to 0.32 ng/mL in non-CDI inflammatory bowel disease patients, representing a statistically significant elevation. 1
PCT levels >0.2 ng/mL demonstrate 81% sensitivity and 73% specificity for severe CDI, with a negative predictive value of 90%, meaning CDI is unlikely to be severe when PCT remains below this threshold. 2
PCT levels >1.1 ng/mL show 85% sensitivity and 88% specificity for predicting CDI in patients with inflammatory bowel disease flares. 1
Clinical Correlation with Severity
PCT elevation strongly associates with CDI severity markers including fever >38°C, acute organ dysfunction, white blood cell count >15,000 cells/mm³, ICU admission, treatment failure, colectomy, and death (OR 3.33,95% CI 1.77-6.23). 2
In multivariable analysis adjusting for age, comorbidities, concurrent bacterial infections, and other confounders, PCT maintains a robust independent association with CDI (OR 4.59,95% CI 2.49-6.70 in IBD patients; OR 3.06,95% CI 1.49-6.26 for expanded severity score). 1, 2
All patients who died from systemic CDI had PCT levels >0.5 ng/mL at admission, and PCT levels were significantly higher in non-survivors compared to survivors. 3
Distinguishing True Infection from Colonization
PCT can differentiate true CDI from C. difficile colonization in ulcerative colitis patients: median PCT was 104.5 pg/mL in patients who responded completely to C. difficile treatment versus 40.3 pg/mL in those who did not respond and had underlying UC flare (p=0.036). 4
PCT elevation indicates active bacterial infection rather than mere colonization, making it particularly valuable in IBD patients where distinguishing disease flare from superimposed CDI is clinically challenging. 4
Important Caveats and Limitations
PCT rises within 4-6 hours of bacterial exposure and peaks at 6-8 hours, so early sampling (<6 hours from symptom onset) may produce false-negative results. 5, 6
PCT has limited sensitivity (35%) but excellent specificity (99%) for systemic infection in emergency department populations, meaning a negative PCT does not rule out CDI, but an elevated PCT strongly suggests bacterial infection. 3
Concurrent acute bacterial infections can confound PCT interpretation, though in multivariable models controlling for this, PCT remains independently associated with CDI severity. 2
PCT does not correlate with fecal C. difficile bacterial burden—intestinal inflammation markers (IL-8, lactoferrin) better predict persistent diarrhea and treatment response than pathogen load. 7
Practical Clinical Algorithm
For suspected CDI in IBD patients: obtain PCT immediately—levels >1.1 ng/mL strongly support CDI diagnosis over disease flare alone. 1
For severity assessment: PCT >0.2 ng/mL indicates potentially severe CDI requiring closer monitoring and consideration for escalated therapy. 2
For colonization versus infection: PCT >100 pg/mL suggests true CDI requiring treatment, while lower levels may indicate colonization in the setting of UC flare. 4
Serial PCT monitoring may guide treatment response, as decreasing levels correlate with effective therapy, though this requires further validation in CDI specifically. 5, 6