What is the role of procalcitonin (PCT) in managing sepsis?

Role of Procalcitonin in Sepsis Management

Procalcitonin (PCT) is a valuable biomarker that can guide antibiotic discontinuation in sepsis patients, reducing antibiotic exposure without increasing mortality, but should not be used alone for initial diagnosis or to withhold antibiotics in patients with high clinical suspicion of infection. 1, 2

Characteristics and Diagnostic Performance

• PCT is a biomarker with normal values <0.05 ng/mL in healthy individuals
• PCT rises approximately 4 hours after bacterial exposure, reaching maximum levels between 6-8 hours
• PCT has a shorter half-life than CRP, allowing for more precise monitoring of treatment response
• PCT has higher diagnostic accuracy for sepsis than CRP:
  • PCT: SROC 0.85, sensitivity 80%, specificity 77%
  • CRP: SROC 0.73, sensitivity 80%, specificity 61% 2

Clinical Applications in Sepsis Management

Antibiotic Stewardship

• PCT-guided antibiotic discontinuation has been shown to:
  • Reduce antibiotic exposure by approximately 1 day 1
  • Decrease the incidence of long-term infection-associated adverse events (7.2% vs 15.3%) 3
  • Lower 28-day mortality (15.2% vs 28.2%) 3
  • Reduce hospitalization costs 3

PCT Interpretation for Clinical Decision-Making

PCT Level	Clinical Interpretation
<0.1 ng/mL	High probability of viral infection or non-infectious condition
0.1-0.25 ng/mL	Low probability of bacterial infection
0.25-0.5 ng/mL	Possible bacterial infection
>0.5 ng/mL	High probability of bacterial infection
>2.0 ng/mL	High probability of sepsis or severe bacterial infection
[2]

Antibiotic Discontinuation Protocol

• PCT levels <0.5 μg/L or a decrease of ≥80% from peak value can guide antibiotic discontinuation once patients are stabilized 1, 2
• The Stop Antibiotics on Procalcitonin Guidance Study demonstrated reduced antibiotic exposure and improved mortality in critically ill patients 1

Important Limitations and Caveats

• PCT should not be used as a stand-alone diagnostic test to rule-in or rule-out sepsis or bacterial infection 4
• PCT should complement, not replace, clinical assessment and microbiological testing 2
• PCT can be elevated in severe viral infections, such as influenza and COVID-19 2
• Decisions to initiate antibiotics should not be based solely on PCT levels, especially in patients with high clinical probability of bacterial infection 1
• Serial measurements of PCT are more valuable than single measurements 2
• PCT-guided therapy has not been well-studied in severely immunocompromised patients 1

Practical Implementation

1. Initial sepsis evaluation: Obtain blood cultures, complete blood count, lactate, and organ function tests as primary diagnostic tests 2

2. PCT measurement: Consider measuring PCT in patients with suspected sepsis with low to intermediate clinical probability of bacterial infection 1

3. Antibiotic initiation: Do not withhold antibiotics based on PCT alone in patients with high clinical suspicion of sepsis 1

4. Monitoring: Perform serial PCT measurements to track treatment response 2

5. Antibiotic discontinuation: Consider stopping antibiotics when:

   • PCT decreases by ≥80% from peak value OR
   • PCT level is <0.5 μg/L AND
   • Patient is clinically stable 1, 2

In summary, while PCT has limitations as a diagnostic tool, it has proven value in guiding antibiotic discontinuation, reducing antibiotic exposure, and improving outcomes in sepsis patients when used as part of a comprehensive clinical assessment.