What is procalcitonin (PCT)?

Procalcitonin (PCT): A Biomarker for Bacterial Infection

Procalcitonin is a precursor hormone of calcitonin that serves as a specific biomarker for bacterial infections, with levels >0.25 ng/mL suggesting bacterial etiology and levels <0.25 ng/mL having high negative predictive value for ruling out bacterial infections, making it valuable for antibiotic stewardship in critically ill patients. 1

Biochemistry and Production

• PCT is a 116-amino acid peptide precursor of the hormone calcitonin
• Normally produced by C cells of the thyroid gland and K cells of the lung 2
• In healthy individuals, PCT is typically undetectable (<0.05 ng/mL) 1
• During bacterial infections, PCT is rapidly produced by parenchymal tissues throughout the body in response to endotoxin 2
• PBMCs (peripheral blood mononuclear cells) can also express PCT when stimulated by bacterial lipopolysaccharides and proinflammatory cytokines 3

Diagnostic Characteristics

• PCT rises approximately 4 hours after bacterial exposure and peaks at 6-8 hours 1
• Clears more quickly as inflammation resolves compared to other inflammatory markers like CRP 1
• Has higher diagnostic accuracy for sepsis compared to CRP:
  • PCT: SROC 0.85, sensitivity 80%, specificity 77%
  • CRP: SROC 0.73, sensitivity 80%, specificity 61% 1

Clinical Interpretation of PCT Levels

PCT Level	Clinical Interpretation
<0.1 ng/mL	High likelihood of viral infection or non-infectious condition
0.1-0.25 ng/mL	Low probability of bacterial infection, antibiotics generally not recommended
0.25-0.5 ng/mL	Possible bacterial infection, consider antibiotics based on clinical assessment
>0.5 ng/mL	High likelihood of bacterial infection, antibiotics recommended
>2.0 ng/mL	High likelihood of sepsis or severe bacterial infection
>10 ng/mL	Severe sepsis or septic shock likely [1]

Clinical Applications

Antibiotic Stewardship

• PCT-guided algorithms safely reduce antibiotic use in respiratory infections 1
• Serial PCT measurements showing declining levels (decrease by ≥80% from peak or <0.25 ng/mL) support safe antibiotic discontinuation 1
• Meta-analyses show PCT-guided therapy reduces antibiotic exposure and improves mortality in critically ill patients 1

Respiratory Infections

• For community-acquired pneumonia (CAP), PCT can help distinguish bacterial from viral etiologies, though no specific threshold perfectly discriminates between them 2
• The American Thoracic Society and Infectious Diseases Society of America recommend using clinical criteria alone rather than PCT plus clinical criteria to decide whether to initiate antibiotics for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) (strong recommendation, moderate-quality evidence) 2

Sepsis and Critical Illness

• PCT has demonstrated value in diagnosing sepsis and monitoring response to therapy 4
• Extremely high PCT levels (>15 μg/L) have been associated with mortality in sepsis-induced multiple organ failure 5

Limitations and Caveats

• Early sampling (<6 hours after admission) may yield false negatives 1
• PCT levels can be influenced by renal function and renal replacement therapy 1
• May be elevated in non-bacterial conditions such as:
  • Severe viral illnesses (influenza, COVID-19)
  • Major trauma or surgery
  • Severe shock or circulatory failure
  • Some autoimmune conditions 1
• No single PCT threshold perfectly discriminates between viral and bacterial pathogens 2
• Sensitivity for bacterial infection ranges from 38% to 91%, underscoring that PCT alone cannot justify withholding antibiotics in suspected bacterial infections 2

Best Practices for PCT Use

• Always interpret PCT in conjunction with clinical assessment and other diagnostic findings 1
• Serial measurements are more valuable than single measurements 1
• For suspected bacterial infections:
  • Obtain baseline PCT measurement
  • Consider withholding antibiotics if PCT <0.25 ng/mL AND clinical suspicion is low
  • Always initiate antibiotics if clinical suspicion is high, regardless of PCT level 1
• For monitoring response to therapy:
  • Measure PCT every 24-48 hours during antibiotic treatment
  • Consider discontinuing antibiotics when PCT decreases by ≥80% from peak or to <0.25 ng/mL 1

PCT represents a valuable tool for diagnosing bacterial infections and guiding antibiotic therapy, but must always be used as part of a comprehensive clinical assessment rather than as a standalone test.