What are the causes of elevated procalcitonin levels?

Causes of Elevated Procalcitonin

Bacterial infections are the primary cause of elevated procalcitonin levels, with higher values seen in sepsis, septic shock, and bacteremia, while non-infectious causes like major surgery, trauma, and certain medical conditions can also increase PCT levels.

Bacterial Infections

Procalcitonin (PCT) is a precursor hormone of calcitonin that serves as a valuable biomarker for bacterial infections. According to guidelines, PCT levels typically correlate with the severity of bacterial infection:

• Bacterial sepsis and septic shock: PCT levels rise significantly in these conditions, with values typically ranging from:

  • Systemic inflammatory response syndrome: 0.6-2.0 ng/mL
  • Severe sepsis: 2-10 ng/mL
  • Septic shock: >10 ng/mL 1

• Bacteremia: Higher PCT values are observed in bacteremic infections compared to non-bacteremic infections 2

• Gram-negative infections: Sites typically infected by gram-negative bacteria show higher PCT values than those infected by gram-positive bacteria 2

• Localized bacterial infections: Even localized bacterial infections can cause PCT elevation, though typically to a lesser degree than systemic infections 1

Non-Infectious Causes

Several non-infectious conditions can also lead to elevated PCT levels:

• Major surgery: PCT can rise transiently following major surgical procedures 3

• Major trauma: Significant tissue injury can trigger PCT elevation 3

• Burns: Extensive burns can cause PCT elevation even without infection 3

• Renal dysfunction: Dialysis-dependent chronic kidney disease is associated with higher baseline PCT values 2

• Certain malignancies: Small cell lung cancer and medullary thyroid carcinoma can cause PCT elevation 4

• Medications: Drugs that stimulate pro-inflammatory cytokine release can increase PCT levels 4

Viral Infections

While PCT was traditionally thought to remain normal in viral infections, more recent evidence shows:

• Severe viral illnesses: Conditions like influenza and COVID-19 can cause PCT elevation, though typically to a lesser degree than bacterial infections 1

• COVID-19: PCT may be elevated in COVID-19 patients without bacterial co-infection (observed in 21% of cases in one study) 1

Clinical Significance and Interpretation

PCT levels should be interpreted in the clinical context:

• Diagnostic value: PCT has superior diagnostic accuracy compared to other inflammatory markers for bacterial infections, with an area under the SROC curve of 0.85, sensitivity of 80%, and specificity of 77% for diagnosing sepsis 3

• Prognostic value: PCT levels correlate with illness severity and can predict outcomes:

  • Persistently elevated PCT in septic shock is associated with higher mortality 5
  • PCT correlates with multiple-organ-failure scores 5

• Monitoring treatment response: Decreasing PCT levels (by ≥80% from peak) indicate appropriate response to antibiotics 3

Important Caveats

• PCT should not be used as the sole criterion for diagnosis or treatment decisions 3
• Interpretation requires consideration of clinical presentation and other laboratory findings 3
• PCT levels <0.25 ng/mL may support withholding antibiotics in patients with low to intermediate probability of bacterial infection 1, 3
• PCT values in healthy individuals are typically less than 0.05 ng/mL 1

Clinical Application

When evaluating elevated PCT levels, consider:

1. Severity assessment: Higher PCT levels generally indicate more severe infection
2. Source identification: Focus on identifying bacterial infection sources, particularly gram-negative infections
3. Treatment guidance: PCT can help guide antibiotic therapy decisions and duration
4. Monitoring: Serial PCT measurements are more valuable than single determinations for assessing treatment response

Remember that while PCT is a valuable tool, it must be interpreted alongside clinical assessment and other diagnostic findings for optimal patient management.