Does a fungal infection increase procalcitonin (PCT) levels?

Fungal Infections Typically Do Not Significantly Elevate Procalcitonin Levels

Fungal infections generally do not cause significant elevations in procalcitonin (PCT) levels, unlike bacterial infections which typically result in marked PCT increases. 1, 2

Procalcitonin Response in Different Types of Infections

• PCT is an inflammatory biomarker that shows marked elevation during bacterial infections but remains at low levels during viral and fungal infections 3, 4
• In bacterial infections, particularly gram-negative infections, PCT levels typically rise to 0.5-2.0 ng/mL in systemic inflammatory response syndrome (SIRS), 2-10 ng/mL in severe sepsis, and >10 ng/mL in septic shock 5
• In invasive fungal infections, PCT levels are typically minimal or not elevated (<0.5 ng/mL) despite the presence of significant infection 1, 2
• PCT rises within 2-3 hours of bacterial infection onset but does not show similar kinetics with fungal pathogens 5, 4

Evidence for Low PCT in Fungal Infections

• A study analyzing 55 episodes of proven or probable invasive fungal infections found that PCT was elevated in only 5.3% of patients with invasive aspergillosis and less than half of invasive candidiasis cases during the early phase of infection 1
• Research examining immunocompromised hematological patients found that those with fungal infections showed minimal or no PCT elevations, while patients with bacterial infections had significantly elevated PCT levels (p < 0.01) 2
• In patients with systemic fungal infections, PCT levels may remain normal or show only moderate elevation (0.5-1.0 ng/mL) even in severe cases 6

Clinical Implications for Differential Diagnosis

• The combination of substantially elevated C-reactive protein (CRP) (100-300 mg/L) with low PCT (<0.5 μg/L) offers good specificity (81%) and sensitivity (85%) for identifying fungal infections in immunocompromised patients 2
• This pattern of inflammatory markers (high CRP with low PCT) can help differentiate fungal from bacterial infections, particularly in immunocompromised patients 2
• PCT levels may have prognostic value in fungal infections, with moderate elevations on day 3 (0.5-1.0 ng/mL) and higher levels (≥1.11 ng/mL) by day 10 potentially indicating an unfavorable course 6

Practical Applications in COVID-19 and Other Clinical Scenarios

• In COVID-19 patients, elevated PCT levels are more indicative of bacterial co-infection rather than the viral infection itself or fungal superinfection 3
• A PCT level <0.25 ng/mL has a high negative predictive value for ruling out bacterial co-infections in COVID-19 patients 3
• Serial PCT measurements are more valuable than single readings, particularly in critically ill or ICU patients under mechanical ventilation, as rising levels may indicate developing bacterial infection 3
• In patients with suspected invasive fungal disease such as COVID-19-associated pulmonary aspergillosis (CAPA), normal or low PCT levels despite clinical deterioration should raise suspicion for fungal rather than bacterial infection 3

Limitations and Caveats

• PCT can be elevated in non-infectious conditions including shock states and certain drug reactions, requiring clinical correlation 5
• In some cases of severe fungal infection with poor outcomes, PCT may show moderate elevation by day 3 and higher levels by day 10, though these elevations are typically less pronounced than in bacterial infections 6
• The diagnostic value of PCT should not be considered in isolation but as part of a comprehensive diagnostic approach including clinical assessment, microbiological cultures, and other biomarkers 3, 7