What is procalcitonin?

What is Procalcitonin?

Procalcitonin (PCT) is a precursor hormone of calcitonin that serves as a biomarker for bacterial infections, rising within 2-3 hours of bacterial exposure and reaching peak levels at 6-8 hours, with concentrations correlating directly with infection severity. 1, 2

Biochemical Origin and Kinetics

• PCT is produced by parafollicular cells of the thyroid gland and neuroendocrine cells of the lung and intestine in response to bacterial infection 2
• In healthy individuals, PCT levels are typically less than 0.05 ng/mL 1, 2
• PCT begins rising approximately 4 hours after bacterial exposure, peaks at 6-8 hours, and has a half-life of 22-35 hours 2, 3
• PCT decreases rapidly after appropriate antibiotic treatment, making it useful for monitoring therapeutic response 2, 4

Clinical Interpretation of PCT Levels

The concentration of PCT correlates with infection severity along a predictable continuum: 1, 3

• <0.05 ng/mL: Normal range in healthy individuals
• 0.5-2.0 ng/mL: Systemic inflammatory response syndrome (SIRS)
• 2.0-10 ng/mL: Severe sepsis
• >10 ng/mL: Septic shock

Diagnostic Performance

• PCT demonstrates 77% sensitivity and 79% specificity for early sepsis diagnosis in critically ill patients 3, 5
• PCT has higher diagnostic accuracy and specificity (77%) compared to C-reactive protein (61%) for bacterial infections 1
• PCT levels <0.5 ng/mL have a high negative predictive value (96-98.6%) for bacterial infections, particularly gram-negative infections 2
• The area under the receiver operating characteristic curve is 0.85 for sepsis diagnosis 5

Clinical Applications in Practice

Antibiotic Stewardship

The Surviving Sepsis Campaign and American College of Critical Care Medicine support using PCT to guide antibiotic duration, with levels <0.5 μg/L or decreases of ≥80% from peak supporting discontinuation in stabilized patients. 1

• PCT-guided antibiotic therapy reduces antibiotic exposure and improves outcomes in critically ill patients 1, 4
• Serial PCT measurements are more valuable than single determinations for monitoring treatment response 1, 2
• The Surviving Sepsis Campaign suggests PCT can support shortening antimicrobial duration in sepsis patients (weak recommendation, low quality evidence) 6

Appropriate Clinical Context

• PCT is most useful when bacterial infection probability is low to intermediate in critically ill patients with new fever and no clear infection focus 1, 2
• PCT should never be used alone to withhold antibiotics in suspected sepsis—empiric antibiotics must be initiated based on clinical suspicion regardless of PCT results 1, 4
• In high-risk individuals or high pretest probability for infection, empiric antibiotic treatment should not be delayed while awaiting PCT results 2

Important Limitations and Pitfalls

False Positives

• PCT may be elevated during severe viral illnesses including influenza and COVID-19, potentially reducing discriminatory power 2, 3
• In COVID-19 patients, PCT may be elevated without bacterial pneumonia in approximately 21% of cases 3
• PCT levels are markedly influenced by renal function and different techniques of renal replacement therapy 3

Diagnostic Constraints

• The Surviving Sepsis Campaign explicitly states no recommendation can be given for using PCT to distinguish severe infection from other acute inflammatory states, as PCT cannot reliably discriminate sepsis from other causes of generalized inflammation 1
• PCT has limited utility in complicated intra-abdominal infections, where an 80% decrease from peak level failed to accurately predict treatment response 1
• No single PCT threshold perfectly discriminates between viral and bacterial pathogens, though higher values strongly correlate with bacterial infection 2

Comparison with C-Reactive Protein

• Unlike PCT, CRP rises more slowly (12-24 hours after inflammatory stimulus) and peaks after 48 hours 2, 3
• CRP is less specific than PCT for bacterial infections but may be more accessible and less expensive 2
• PCT rises earlier (4 hours) than CRP (12-24 hours) after an inflammatory stimulus 3
• PCT is not typically elevated in chronic inflammatory states, making it more specific for acute bacterial infections 3

Optimal Clinical Algorithm

When using PCT in clinical practice, follow this evidence-based approach: 1

1. Perform thorough clinical evaluation and obtain appropriate cultures before antimicrobial therapy
2. Measure PCT levels as part of initial workup in patients with suspected sepsis
3. Initiate empiric antibiotics based on clinical suspicion regardless of PCT results
4. Use serial PCT measurements to monitor treatment response
5. Consider antibiotic discontinuation when PCT levels decrease to <0.5 μg/L or drop ≥80% from peak in stabilized patients
6. Always interpret PCT in conjunction with clinical judgment—never as the sole decision-making tool