What is the use of procalcitonin (PCT) and C-reactive protein (CRP) and when should these tests be ordered?

Use of Procalcitonin (PCT) and C-Reactive Protein (CRP) in Clinical Practice

PCT and CRP should be ordered selectively based on the clinical scenario, with PCT being more useful for bacterial infection detection and antibiotic stewardship, while CRP serves as a general inflammatory marker with lower specificity but greater availability.

Characteristics and Kinetics

Procalcitonin (PCT)

• PCT is a precursor hormone of calcitonin produced by the thyroid gland's parafollicular cells and neuroendocrine cells in the lung and intestine 1
• PCT rises rapidly within 4 hours after bacterial exposure, peaks at 6-8 hours, and has a half-life of 22-35 hours 1
• Normal values in healthy individuals are <0.05 ng/mL 1
• PCT is more specific for bacterial infections compared to CRP, with diagnostic accuracy showing an area under the ROC curve of 0.85 1, 2
• PCT levels correlate with infection severity and decrease rapidly after effective antibiotic treatment 1, 3

C-Reactive Protein (CRP)

• CRP is an acute-phase protein synthesized by the liver in response to inflammation or infection 1
• CRP rises more slowly, starting 12-24 hours after inflammatory stimulus, with peak values at 48 hours 1
• Normal CRP levels are typically <5 mg/L with a common cutoff value of 10 mg/L 1
• CRP has lower specificity than PCT for bacterial infections, with an area under the ROC curve of 0.73 1
• CRP levels can be affected by neutropenia, immunodeficiency, and use of nonsteroidal anti-inflammatory drugs 1

Clinical Indications for Testing

When to Order PCT

• Low to intermediate probability of bacterial infection in critically ill patients with new fever and no clear focus of infection 1
• To guide decisions about antibiotic discontinuation, especially in ICU settings 1, 2
• For differentiating bacterial from viral respiratory infections 1, 3
• For monitoring response to antibiotic therapy in severe infections 1, 2
• In suspected sepsis when rapid decision-making about antibiotics is needed 1, 2

When to Order CRP

• Low to intermediate probability of bacterial infection in critically ill patients with new fever and no clear focus of infection 1
• As an adjunct to clinical assessment in community-acquired pneumonia (CRP >100 mg/L makes pneumonia likely) 1
• For monitoring the inflammatory response over time in various conditions 1
• In resource-limited settings where PCT may not be available 2, 4
• For initial assessment of infection severity in primary care settings 1

When NOT to Order These Tests

• High probability of bacterial infection - biomarkers should not delay antibiotic administration 1
• Routine use in sepsis and septic shock is not recommended 1
• As standalone tests without clinical context 1
• In patients already receiving antibiotics (may affect interpretation) 1
• For definitive diagnosis of meningitis (though may be helpful as adjuncts) 1

Comparative Performance and Clinical Utility

• PCT has higher specificity (77%) than CRP (61%) for bacterial infections 1, 2
• PCT correlates better with severity scores (APACHE II, SOFA) than CRP 2
• PCT-guided algorithms have been shown to safely reduce antibiotic use in respiratory infections and critical care 1, 2
• Combined use of PCT and CRP increases specificity for infection to 82.3% 4
• PCT is particularly elevated in bacteremia and septic shock compared to localized infections 4

Special Considerations

• In COVID-19 patients, PCT <0.25 mg/L can help rule out bacterial co-infection in non-ICU hospitalized patients 5
• PCT may be elevated during severe viral illnesses including influenza and COVID-19, potentially reducing its discriminatory power 1
• CRP is more widely available and less expensive than PCT, making it more accessible in resource-limited settings 3, 4
• Neither biomarker should replace clinical judgment or delay antibiotic administration in critically ill patients 1
• Serial measurements are often more valuable than single determinations 1

Recommended Approach to Testing

1. Assess pre-test probability of bacterial infection based on clinical presentation
2. For low-to-intermediate probability scenarios, order either PCT or CRP (or both if available) 1
3. Consider PCT if available for antibiotic stewardship decisions 1, 2
4. Interpret results in context of clinical findings and other laboratory data 1
5. Use serial measurements to monitor treatment response and guide antibiotic duration 1, 2