Which Fungal Infections Can Cause Elevated Procalcitonin (PCT) Levels?
Fungal infections generally do NOT cause significant PCT elevation, but invasive candidiasis can cause modest PCT increases (0.5-1.0 ng/mL), while invasive aspergillosis rarely elevates PCT at all. 1, 2, 3
Key Diagnostic Pattern: Low PCT with High CRP Suggests Fungal Infection
In immunocompromised patients, the combination of substantially elevated CRP (100-300 mg/L) together with low PCT (<0.5 μg/L) strongly suggests systemic fungal infection, with 81% specificity and 85% sensitivity. 3
This pattern is particularly valuable because it helps differentiate fungal from bacterial infections in critically ill patients where the distinction is clinically crucial 3.
Specific Fungal Infections and PCT Levels
Invasive Candidiasis (Candidemia)
- PCT levels remain low (median 0.71 ng/mL, IQR 0.5-1.1) in candidemia, significantly lower than bacterial sepsis (median 12.9 ng/mL). 2
- In the early phase of invasive candidiasis, PCT is elevated in fewer than half of episodes 1
- A PCT value <2 ng/mL has a 94% negative predictive value for ruling out bacteremia and a similar positive predictive value for candidemia in critically ill surgical patients 2
- In severe fungal infections with unfavorable outcomes, PCT may show moderate elevation (0.5-1.0 ng/mL) on day 3, with higher levels (≥1.11 ng/mL) appearing by day 10 4
Invasive Aspergillosis
- PCT elevation occurs in only 5.3% of patients with invasive aspergillosis, making it essentially unhelpful for diagnosis. 1
- Due to extremely low sensitivity and specificity, PCT adds little to the diagnosis of invasive aspergillosis 1
COVID-19-Associated Pulmonary Aspergillosis (CAPA)
- The incidence of CAPA ranges from 10.2% to 14.9% in patients with severe COVID-19 5
- In COVID-19 patients, PCT interpretation is confounded by hyperinflammatory status or cytokine storm, which may result in higher PCT production than in other viral pneumonias 5
- Modified AspICU or ECMM/ISHAM consensus criteria are recommended for CAPA diagnosis, not PCT levels 5
Clinical Application Algorithm
When You See Low PCT in a Septic Patient:
If PCT <2 ng/mL in critically ill surgical patient with sepsis → strongly consider candidemia over bacteremia 2
If PCT <0.5 μg/L AND CRP 100-300 mg/L in immunocompromised patient → suspect systemic fungal infection 3
If PCT remains low despite clinical deterioration → fungal infection is more likely than bacterial 1, 2
Prognostic Value in Fungal Infections:
- PCT levels correlate with severity and outcome of systemic fungal infection 4
- Higher PCT levels (≥1.11 ng/mL) by day 10 indicate unfavorable course 4
- Normal or moderately elevated PCT on day 10 suggests better prognosis 4
Critical Caveats
- The primary utility of PCT in fungal infections is its ABSENCE rather than its presence - low PCT helps rule out bacterial co-infection 1, 2, 3
- In patients with bacterial infection, PCT is significantly elevated (especially with gram-negative bacteria), whereas fungal infections show minimal or no PCT elevation 3, 6
- Serial PCT measurements are more valuable than single readings, particularly in immunocompromised patients 5, 4
- Early sampling (<6 hours from admission) may produce false-negative results 5
- PCT is most diagnostically valuable for bacterial infections in immunocompromised patients with hematologic malignancy 6