What is the role of procalcitonin (PCT) in guiding antibiotic therapy in patients with suspected or confirmed bacterial infections and sepsis?

Role of Procalcitonin in Guiding Antibiotic Therapy in Bacterial Infections and Sepsis

Procalcitonin (PCT) should be used to guide antibiotic discontinuation in patients with suspected or confirmed bacterial infections and sepsis, as low PCT levels (<0.5 μg/L) or a decrease of ≥80% from peak value can safely support antibiotic discontinuation decisions once patients are clinically stable. 1

PCT as a Biomarker for Bacterial Infections

PCT is a host-response biomarker that rises in proportion to the severity of bacterial inflammatory response:

• Normal value: <0.05 ng/mL
• 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 1

PCT has several advantages over traditional inflammatory markers:

• Rises 4 hours after bacterial exposure, peaks at 6-8 hours
• Higher diagnostic accuracy for sepsis (sensitivity 80%, specificity 77%) compared to CRP (sensitivity 80%, specificity 61%) 1
• Helps differentiate bacterial from non-bacterial infections and inflammatory states 2

Evidence-Based Algorithm for PCT-Guided Antibiotic Therapy

For Patients with Suspected Sepsis:

1. Do not delay antibiotics while waiting for PCT results in patients with suspected sepsis 1
2. Initiate empiric antibiotics in high-risk individuals and/or those with high pretest probability for infection regardless of PCT level 2
3. Monitor PCT levels to track infection resolution
4. Consider antibiotic discontinuation when:
   • PCT <0.5 μg/L or decreases by ≥80% from peak value
   • Patient is clinically stable 1, 3

For Patients with Respiratory Infections:

1. Low-risk, stable patients:
   • PCT <0.25 μg/L: Consider withholding antibiotics 3
   • PCT >0.25 μg/L: Consider initiating antibiotics
2. Monitor PCT levels during treatment
3. Consider discontinuing antibiotics when PCT decreases to <0.25 μg/L or by ≥80% from peak 1, 2

Clinical Benefits of PCT-Guided Therapy

• Reduces antibiotic exposure by approximately 1 day 1
• Two-fold reduction in antibiotic use without increased mortality when limiting antibiotics in patients with PCT <0.25 ng/mL 1
• May reduce both antibiotic exposure and mortality in critically ill patients 3

Important Caveats and Limitations

• Do not use PCT alone to make antibiotic decisions:

  • Combine with careful patient assessment and clinical algorithms 2
  • Serial measurements are more valuable than single measurements 1
  • PCT should complement, not replace, clinical assessment and microbiological testing 1

• Continue antibiotics regardless of PCT in:

  • Severely immunocompromised patients
  • Infections requiring prolonged treatment (e.g., endocarditis)
  • Undrained infection sources 1
  • Patients with high clinical probability of bacterial infection 1

• American Thoracic Society and Infectious Diseases Society of America caution: PCT alone cannot justify withholding antibiotics from patients with community-acquired pneumonia (sensitivity ranges from 38% to 91%) 1

Implementation Considerations

• PCT-guided therapy should be implemented with continuous notification and regular feedback from all antibiotic stewardship stakeholders 2
• Future research should examine optimal implementation strategies, real-world impact on clinical outcomes and costs, and applicability to immunocompromised patients 3