What are the causes of elevated procalcitonin (PCT) levels?

Causes of Procalcitonin Elevation

Procalcitonin (PCT) is primarily elevated in bacterial infections, with levels increasing dramatically by hundreds to thousands of fold within 4-6 hours after bacterial exposure, while typically remaining low in viral infections and non-infectious inflammatory conditions. 1

Primary Causes of PCT Elevation

Bacterial Infections

• Severe bacterial infections - highest elevations
  • Sepsis and septic shock (>10 ng/mL) 1
  • Bacterial meningitis 2, 3
  • Severe pneumonia 4
  • Bacteremia/septicemia 5
  • Severe soft tissue infections 1

Correlation with Infection Severity

PCT levels correlate with infection severity 1:

• <0.1 ng/mL: Likely viral infection or non-infectious condition
• 0.1-0.25 ng/mL: Low probability of bacterial infection
• 0.25-0.5 ng/mL: Possible bacterial infection

• 0.5 ng/mL: High likelihood of bacterial infection

• 2.0 ng/mL: High likelihood of sepsis or severe bacterial infection

• 10 ng/mL: Severe sepsis or septic shock likely

Non-Bacterial Causes of PCT Elevation

Viral Infections with Bacterial Co-infection

• Influenza with bacterial superinfection 4
• Note: PCT may not be elevated with concurrent viral and bacterial infection in some cases 4

Severe COVID-19

• Elevated PCT in severe COVID-19 may occur independently of bacterial co-infection 6
• Higher PCT levels in COVID-19 are associated with:
  • Need for mechanical ventilation
  • Longer duration of ventilation
  • Higher mortality

Other Non-Infectious Causes

• Major surgery or trauma
• Severe burns
• Cardiogenic shock 7
• Circulatory failure 7

Important Clinical Considerations

Diagnostic Accuracy

• PCT has higher specificity (93%) for bacterial infections compared to CRP 1
• PCT rises and falls more quickly than CRP, allowing for more timely diagnosis and monitoring 1
• PCT has higher diagnostic accuracy for sepsis (sensitivity 80%, specificity 77%) compared to CRP (sensitivity 80%, specificity 61%) 1

Potential False Negatives

• Early sampling (<6 hours after admission) may yield false negatives 1
• Infections with certain pathogens like Legionella and Mycoplasma may not elevate PCT 4
• Some cases of bacterial meningitis may not show PCT elevation 2

Potential False Positives

• Renal dysfunction can influence PCT levels 1
• Renal replacement therapy may affect PCT measurements 1

Clinical Interpretation

• PCT should never be used as a standalone test 1
• Results must be interpreted alongside clinical assessment and other diagnostic findings 1
• Serial measurements showing trends are more valuable than single measurements 1
• PCT can help guide antibiotic therapy decisions, including when to discontinue antibiotics 1

Comparison with Other Inflammatory Markers

PCT offers several advantages over other inflammatory markers:

• More specific for bacterial infections than CRP 5
• Faster rise and fall than CRP (rises within 4 hours vs. 12-24 hours for CRP) 1
• Better at distinguishing bacterial from viral infections compared to white blood cell count and CRP 5, 3
• Independent predictor of mortality in critically ill patients 7

When evaluating a patient with elevated PCT, consider the clinical context, timing of measurement, and other laboratory and clinical findings to determine the most likely cause of elevation.