What is procalcitonin?

What is Procalcitonin?

Procalcitonin (PCT) is a 116 amino acid precursor protein of the hormone calcitonin that serves as a biomarker to differentiate bacterial infections from viral infections and non-infectious inflammatory conditions, with levels rising within 4 hours of bacterial exposure and peaking at 6-8 hours. 1, 2

Biochemical Structure and Normal Physiology

• PCT is normally produced by parafollicular C-cells of the thyroid gland and neuroendocrine cells of the lung and intestine 1
• In healthy individuals, PCT levels are undetectable, typically less than 0.05 ng/mL 1, 2
• The protein consists of 114-116 amino acids with a molecular weight of approximately 13 kDa 3, 4, 5

Mechanism During Infection

• When stimulated by bacterial endotoxin and inflammatory cytokines (TNF-α, IL-6, IL-8), PCT is rapidly produced by parenchymal tissue throughout the body, not just the thyroid 1, 6
• PCT begins rising approximately 4 hours after bacterial exposure, reaches maximum levels at 6-8 hours, and decreases rapidly after appropriate antibiotic treatment 1, 2
• The production is upregulated in bacterial infections and downregulated by viral infections, though this distinction is not absolute 4

Clinical Interpretation by Level

The severity of infection correlates with PCT concentration 2, 7, 6:

• <0.05 ng/mL: Normal range in healthy individuals
• 0.1-0.25 ng/mL: Low probability of bacterial infection but cannot completely rule it out
• 0.25-0.5 ng/mL: Possible bacterial infection
• >0.5 ng/mL: Increased likelihood of bacterial infection
• 0.6-2.0 ng/mL: Systemic inflammatory response syndrome (SIRS)
• 2.0-10 ng/mL: Severe sepsis
• >10 ng/mL: Septic shock

Primary Clinical Applications

PCT is most valuable for guiding antibiotic discontinuation decisions rather than initiation, particularly in critically ill patients. 1, 2, 7

• In patients with low to intermediate probability of bacterial infection, PCT measurement combined with clinical evaluation can help rule out bacterial infection 1, 2
• Serial PCT measurements (every 24-48 hours) are more valuable than single readings for monitoring treatment response 2, 7, 6
• A decrease of >25% or >80% from peak PCT levels indicates effective treatment and supports antibiotic discontinuation 2, 6
• A 50% rise in PCT from baseline is more predictive of secondary bacterial infection than absolute values in critically ill patients 7, 6

Critical Limitations and Pitfalls

PCT should never be used alone to decide whether to initiate or withhold antibiotics, as it has variable sensitivity (38-91%) and can be elevated in non-bacterial conditions. 1, 2, 7

False Positive Scenarios:

• Severe viral illnesses including influenza and COVID-19 (approximately 21% of COVID-19 patients without bacterial co-infection have elevated PCT) 1, 2, 7, 6
• Shock states including cardiogenic and hemorrhagic shock 7
• Acute respiratory distress syndrome (ARDS) 6
• Drug hypersensitivity reactions 7

False Negative Scenarios:

• Early sampling (<6 hours from symptom onset) may produce false-negative results as PCT requires time to rise 7, 6
• Certain pathogens like Legionella and Mycoplasma may not elevate PCT despite active infection 1

Comparison with C-Reactive Protein (CRP)

• PCT rises faster than CRP (4 hours vs 12-24 hours) and peaks earlier (6-8 hours vs 48 hours) 1, 2, 6
• PCT has higher specificity for bacterial infections (77-83%) compared to CRP (61%) 1, 6
• CRP is less expensive and more widely available but less specific for bacterial etiology 1, 2
• Unlike PCT, CRP concentrations can be affected by neutropenia, immunodeficiency, and nonsteroidal anti-inflammatory drugs 1

Evidence-Based Recommendations for Use

In high-risk patients or those with high pretest probability for infection, empiric antibiotic treatment should never be delayed while awaiting PCT results. 2, 7

• For suspected hospital-acquired or ventilator-associated pneumonia, use clinical criteria alone rather than PCT plus clinical criteria to decide whether to initiate antibiotics 1
• For severe acute pancreatitis, PCT may be valuable in predicting the risk of developing infected pancreatic necrosis 1
• In critically ill patients with new fever and no clear focus, measure PCT only when probability of bacterial infection is low to intermediate 1
• PCT is most appropriate for antibiotic de-escalation and discontinuation decisions, not initiation 7