What is the role of serum procalcitonin (PCT) in diagnosing and managing fungal infections?

Serum Procalcitonin in Fungal Infection

Direct Answer

Serum procalcitonin (PCT) remains low or normal in fungal infections and should NOT be used as a primary diagnostic marker for invasive fungal disease. 1 Instead, low PCT levels (<0.25-0.5 ng/mL) combined with substantially elevated C-reactive protein (CRP >100-300 mg/L) should raise clinical suspicion for fungal rather than bacterial infection. 1, 2

Diagnostic Performance and Limitations

PCT Response in Fungal vs. Bacterial Infections

• PCT shows minimal elevation in fungal infections, with sensitivity as low as 5.3% for invasive aspergillosis and less than 50% for invasive candidiasis in the early phase. 3

• In bacterial infections, PCT rises significantly: 0.5-2.0 ng/mL in SIRS, 2-10 ng/mL in severe sepsis, and >10 ng/mL in septic shock, whereas fungal infections typically maintain levels <0.5 ng/mL. 1

• The diagnostic pattern that suggests fungal infection is substantially elevated CRP (100-300 mg/L) combined with low PCT (<0.5 μg/L), which offers 81% specificity, 85% sensitivity, 73% positive predictive value, and 89% negative predictive value for fungal infections in immunocompromised patients. 2

Clinical Applications

In COVID-19-associated infections, normal or low PCT levels despite clinical deterioration should raise suspicion for COVID-19-associated pulmonary aspergillosis (CAPA) rather than bacterial superinfection. 1 Elevated PCT in COVID-19 patients is more indicative of bacterial co-infection than fungal superinfection. 4

For ruling out bacterial co-infection, PCT <0.25 ng/mL has high negative predictive value, which indirectly supports considering alternative diagnoses including fungal infection when patients deteriorate despite low PCT. 4, 1

Prognostic Value

• PCT may have limited prognostic utility in fungal infections. One small study showed moderately elevated PCT (0.5-1.0 ng/mL) on day 3 and higher levels (≥1.11 ng/mL) on day 10 correlated with unfavorable outcomes in severe fungal infections, but this requires validation in larger cohorts. 5

• PCT cannot replace definitive diagnostic methods such as fungal cultures, galactomannan testing, beta-D-glucan, or imaging for invasive fungal disease. 4, 1

Practical Algorithm for Clinical Use

When evaluating a critically ill patient with suspected infection:

1. Measure both PCT and CRP at presentation and serially during hospitalization. 4, 1

2. If PCT is low (<0.5 ng/mL) but CRP is substantially elevated (>100 mg/L), consider invasive fungal infection and pursue fungal-specific diagnostics (galactomannan, beta-D-glucan, fungal cultures, imaging). 1, 2

3. If PCT is significantly elevated (>0.5 ng/mL), bacterial infection is more likely; pursue bacterial cultures and consider empirical antibacterial therapy. 4

4. Do not withhold antifungal therapy based on low PCT alone when clinical suspicion for invasive fungal disease is high based on risk factors (immunosuppression, prolonged neutropenia, corticosteroid use) and clinical/radiographic findings. 1

Critical Caveats

• PCT can be elevated in non-infectious conditions including shock states and certain drug reactions, requiring clinical correlation rather than relying on biomarkers alone. 1

• Early PCT sampling (<6 hours of admission) may yield false-negative results for bacterial infections, potentially leading to misinterpretation when considering fungal etiologies. 4

• The combination of biomarkers is more valuable than single measurements, and all results must be interpreted within the complete clinical context including physical examination findings (such as fundoscopy for candidal endophthalmitis), imaging, and microbiological data. 4, 1