What is the role of procalcitonin (PCT) in guiding antibiotic therapy for suspected sepsis?

Procalcitonin in Sepsis: Role in Antibiotic Stewardship

Procalcitonin should NOT be used to withhold antibiotics in suspected sepsis, but rather to guide antibiotic discontinuation once patients stabilize, with PCT levels <0.5 µg/L or decreases ≥80% from peak levels supporting cessation of therapy. 1

Initial Management: Never Delay Antibiotics

• In ICU patients with suspected sepsis, clinicians must not initially withhold antibiotics based on PCT levels, regardless of how low the value is. 1
• Antibiotics should be administered within one hour of sepsis recognition, with appropriate cultures obtained beforehand if this does not cause significant delay. 2, 3
• PCT serves only as supportive and complementary information to clinical assessment—decisions on initiating antimicrobial therapy should never be made solely based on PCT levels. 1

Diagnostic Value: When to Measure PCT

Measure PCT in critically ill patients with new fever and no clear focus of infection when the clinical probability of bacterial infection is low to intermediate—not when probability is high. 1, 2

Diagnostic Performance

• PCT has superior diagnostic accuracy compared to CRP for bacterial infections, with specificity of 77% versus 61% for CRP. 2
• The area under the ROC curve for PCT in sepsis diagnosis is 0.85, with sensitivity of 80% and specificity of 77%. 1
• PCT rises within 2-3 hours of bacterial infection onset, reaching maximum levels after 6-8 hours, making it more rapid than CRP. 2

Interpretation by Severity

• Healthy individuals: <0.05 ng/mL 2
• SIRS: 0.6-2.0 ng/mL 2
• Severe sepsis: 2-10 ng/mL 2
• Septic shock: >10 ng/mL 2

Antibiotic Discontinuation: The Primary Role

PCT-guided antibiotic discontinuation reduces both antibiotic exposure and mortality in critically ill patients. 1

Specific Discontinuation Criteria

Use PCT to guide antibiotic cessation when BOTH of the following are met:

• Patient has clinically stabilized 1
• PCT level is <0.5 µg/L OR has decreased ≥80% from peak levels 1, 2

Evidence for Improved Outcomes

• A meta-analysis of 11 RCTs involving 4,482 patients demonstrated that PCT-guided therapy resulted in improved survival and lower antibiotic treatment duration. 1
• The largest systematic review of 16 studies with >5,000 patients showed PCT-guided discontinuation decreased antibiotic utilization by 1 day and improved mortality, though evidence certainty was low due to risk of bias. 1
• The Stop Antibiotics on Procalcitonin Guidance Study specifically demonstrated reductions in both antibiotic exposure and mortality. 1

Serial Monitoring Strategy

Serial PCT measurements are more valuable than single determinations for monitoring treatment response. 2

• Obtain baseline PCT at time of sepsis recognition (T0) 2
• Repeat measurements at 24 hours (T24) and 96 hours (T96) to assess trajectory 2
• A mean percentage reduction of >44% suggests bacterial infection responding to therapy 4
• Daily assessment for de-escalation should incorporate PCT trends alongside clinical improvement 3

Critical Limitations and Pitfalls

When PCT May Be Misleading

• Severely immunocompromised patients were excluded from most PCT trials—use with extreme caution in this population. 1
• PCT can be elevated in severe viral illnesses and non-infectious conditions (trauma, surgery, pancreatitis). 2
• PCT levels can be affected by neutropenia, immunodeficiency, and nonsteroidal anti-inflammatory drugs. 1
• PCT alone cannot effectively distinguish bacterial versus viral infections—clinical context is essential. 5

Populations Where PCT Should NOT Guide Initial Therapy

• Patients with high clinical probability of bacterial infection 1, 2
• Patients with dyspnea and suspected/known heart disease 2
• Patients with fever alone without other clinical features 2

Practical Algorithm for PCT Use in Sepsis

1. Suspected sepsis identified → Obtain cultures and start antibiotics within 1 hour (do NOT wait for PCT) 1, 3

2. Measure baseline PCT as part of initial workup for low-to-intermediate probability bacterial infection 2

3. Continue antibiotics regardless of initial PCT value until patient stabilizes 1

4. Once patient stabilizes (typically 3-5 days):

   • Check repeat PCT level 1, 3
   • If PCT <0.5 µg/L OR decreased ≥80% from peak → Consider discontinuation 1, 2
   • If PCT remains elevated → Continue therapy and reassess daily 3

5. Typical treatment duration: 7-10 days, with longer courses for slow clinical response, undrainable foci, S. aureus bacteremia, or fungal/viral infections 3

Comparison with CRP

When choosing between PCT and CRP, current guidelines do not strongly favor one over the other, though PCT has higher diagnostic accuracy (85% vs 73% area under ROC curve) and rises more rapidly. 1, 2

• CRP rises more slowly than PCT and peaks later, making it less useful for early decision-making 2
• Combined use of PCT with other clinical and laboratory parameters provides optimal decision-making 2