PATHCHAT Edition No. 47
June 2018
Please contact your local Ampath pathologist for more information.
Compiled by: Dr. C. Kingsburgh
Introduction
🔹 Why Are Sepsis Biomarkers Important?
- Sepsis diagnosis remains challenging due to delays in blood culture results and potential false positives/negatives.
- Every hour delay in initiating appropriate therapy increases mortality by 7%.
- Biomarkers such as CRP and PCT offer potential early detection tools.
✅ Commonly Used Sepsis Biomarkers:
- C-reactive protein (CRP).
- Procalcitonin (PCT).
📌 CRP and PCT differ in their properties, sensitivity, specificity, and clinical applications.
What Are CRP & PCT?
🔹 C-Reactive Protein (CRP):
- An acute phase protein synthesized in the liver in response to IL-6 during infections or inflammatory conditions.
- Rises within 24–48 hours of infection and remains elevated for several days.
- Non-specific marker of inflammation (not exclusive to bacterial infections).
🔹 Procalcitonin (PCT):
- The precursor of calcitonin, normally synthesized by thyroid C-cells.
- During bacterial infections, multiple tissues produce PCT, leading to a systemic rise in levels.
- Rises much earlier (4–12 hours) compared to CRP (24–48 hours).
- Highly specific to bacterial infections.
📌 PCT is less affected by viral infections and autoimmune diseases compared to CRP.
CRP vs. PCT: Which One to Choose?
✅ Comparative Analysis of CRP & PCT in Bacterial Sepsis:
✔ Sensitivity & Specificity:
- PCT has higher sensitivity (77%) and specificity (79%) for bacterial septicaemia compared to CRP (75% and 67%).
✔ Response Time:
- PCT rises within 4–12 hours, CRP takes 24–48 hours.
✔ Prognostic Value:
- PCT correlates with bacterial load and severity of infection.
- CRP does not correlate with severity.
✔ Monitoring Treatment Response:
- PCT has a half-life of 24–35 hours, making daily measurements clinically useful.
- A 30–50% daily drop in PCT suggests effective infection control.
- CRP has a longer half-life (~48 hours), limiting its utility in daily monitoring.
✔ Guiding Antibiotic Therapy Duration:
- Multiple ICU studies confirm that PCT-guided therapy reduces antibiotic duration and improves mortality.
- In PCT-based protocols, antibiotics are stopped when PCT levels decrease by 80% from peak or fall below 0.5 ng/mL.
📌 PCT is a superior biomarker for early sepsis detection, prognosis, and treatment monitoring.
Indications for CRP & PCT
✅ When to Use CRP:
- To assess bacterial involvement in COPD exacerbations (Type II & III).
- In the emergency department for uncertain community-acquired pneumonia (CAP) diagnosis.
✅ When to Use PCT:
- To differentiate bacterial sepsis from non-infectious systemic inflammatory response syndrome (SIRS).
- To assess sepsis severity (prognostic marker).
- To monitor response to therapy.
- To guide antibiotic discontinuation in systemic bacterial infections.
- To exclude bacterial CAP and acute COPD exacerbations if PCT <0.25 ng/mL.
📌 South African CAP guidelines state that CRP or PCT can be used in emergency settings where pneumonia diagnosis is uncertain.
Pros & Cons of CRP vs. PCT
🔹 Strengths of CRP:
✅ Cheaper than PCT.
✅ Not affected by renal disease or dialysis.
✅ More likely to be elevated in fungal infections (e.g., invasive candidiasis).
🔹 Limitations of CRP:
🚨 Elevated by non-bacterial causes:
- Trauma, surgery, autoimmune diseases.
- Not useful for monitoring bacterial load.
- Slower response time (peaks at 24–48 hours).
🔹 Strengths of PCT:
✅ Higher sensitivity and specificity than CRP.
✅ Rises quickly (4–12 hours) and clears faster (24–35 hours).
✅ Excellent for monitoring sepsis progression.
✅ Not elevated by viral infections, most autoimmune diseases, or transplant rejection.
🔹 Limitations of PCT:
🚨 Elevated by non-bacterial conditions:
- Severe trauma, burns, pancreatitis, prolonged cardiogenic shock.
- Certain autoimmune diseases (e.g., Kawasaki disease, Goodpasture’s syndrome).
🚨 More expensive than CRP.
📌 PCT is a better biomarker for bacterial sepsis but is costly and may not be suitable for all clinical settings.
Conclusion
✅ CRP and PCT are both useful sepsis biomarkers but have different applications.
✅ PCT is superior for early diagnosis, severity assessment, and monitoring treatment response.
✅ CRP is cheaper and useful for screening bacterial infections in conditions like COPD exacerbations.
✅ PCT-guided antibiotic therapy has been proven to reduce antibiotic use and hospital stay.
📌 Choosing between CRP and PCT depends on the clinical context, cost considerations, and required diagnostic accuracy.