What causes elevated procalcitonin levels?

Causes of Elevated Procalcitonin

Bacterial infections are the primary cause of significantly elevated procalcitonin levels, with higher values correlating with infection severity from systemic inflammatory response syndrome to septic shock. 1

Primary Causes of Elevated Procalcitonin

Bacterial Infections

• Sepsis and septic shock: PCT levels increase proportionally with infection severity:
  • Systemic inflammatory response syndrome: 0.6-2.0 ng/mL
  • Severe sepsis: 2-10 ng/mL
  • Septic shock: >10 ng/mL 1
• PCT rises rapidly (within 2-3 hours) after bacterial infection onset 1
• PCT correlates with severity of infection and decreases rapidly after effective antibiotic treatment 1

COVID-19 and Other Severe Viral Infections

• Recent studies show PCT may be elevated during severe viral illnesses including influenza and COVID-19 1
• However, viral infections typically cause less pronounced PCT elevation compared to bacterial infections 2

Other Causes

• Major trauma
• Major surgery
• Burns
• Treatment with drugs that stimulate pro-inflammatory cytokine release
• Certain malignancies:
  • Small cell lung cancer
  • Medullary thyroid carcinoma 3

Clinical Significance

Diagnostic Value

• PCT is a valuable biomarker for distinguishing bacterial from viral or non-infectious inflammatory conditions 2
• PCT has higher specificity for bacterial infection than C-reactive protein (CRP) 4
• PCT levels <0.1 ng/mL make severe bacterial infection unlikely (sensitivity 91%, negative predictive value 86%) 5
• PCT levels >0.5 ng/mL suggest bacterial infection is likely (specificity 79%, positive predictive value 61%) 5

Prognostic Value

• Persistently elevated PCT levels in septic patients correlate with poor outcomes 4
• PCT values exceeding 15 μg/L have been observed in patients who died of sepsis-induced multiple organ failure 6
• PCT correlates with multiple-organ-failure scores, making it valuable for monitoring disease progression 4

Antimicrobial Stewardship Applications

• PCT can guide antibiotic therapy decisions:
  • Support shortening antibiotic duration in sepsis patients 1
  • Support discontinuation of empiric antibiotics when clinical evidence of infection is limited 1
  • Help distinguish COVID-19 from bacterial pneumonia 1

Important Caveats

• PCT should not be used in isolation but interpreted alongside clinical assessment 1
• PCT may be falsely elevated in certain non-infectious conditions (trauma, surgery, burns) 3
• In critically ill patients with high probability of bacterial infection, PCT should not be used to rule out infection 1
• PCT levels can be affected by:
  • Timing of measurement (peaks 6-8 hours after infection onset) 1
  • Prior antibiotic administration (may lower values) 1
  • Renal dysfunction (may elevate values)

Clinical Algorithm for Interpreting Elevated PCT

1. Assess PCT level:

   • <0.5 ng/mL: Bacterial infection unlikely
   • 0.5-2.0 ng/mL: Consider localized bacterial infection
   • 2-10 ng/mL: Consider severe sepsis

   • 10 ng/mL: Consider septic shock

2. Rule out non-infectious causes if PCT is elevated:

   • Recent surgery/trauma (within 24-48 hours)
   • Burns
   • Certain malignancies
   • Medication effects

3. Correlate with other clinical and laboratory findings:

   • Physical examination findings
   • White blood cell count
   • CRP (less specific but may be used in conjunction)
   • Microbiological cultures

4. Monitor trends rather than single values:

   • Decreasing values suggest improving infection control
   • Persistently elevated or increasing values suggest treatment failure or developing complications

Remember that while PCT is a valuable biomarker, clinical judgment remains essential in interpreting its values and making treatment decisions.