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

Value of Procalcitonin in Infant Sepsis

Procalcitonin (PCT) is a valuable biomarker in infant sepsis that can be used to support the discontinuation of empiric antibiotics in infants who initially appeared to have sepsis but subsequently have limited clinical evidence of infection, and can help guide the duration of antimicrobial therapy.

Diagnostic Value of PCT in Infant Sepsis

Sensitivity and Specificity

• PCT shows high sensitivity (87-100%) at a cut-off value of 0.5 ng/mL for diagnosing bacterial sepsis in neonates, though specificity varies considerably 1
• Typical values for interpretation:
  • <0.5 ng/ml: Suggests noninfectious inflammation

  • 2.0 ng/ml: Strongly suggests bacterial sepsis 2

Comparison with Other Biomarkers

• PCT performs better than C-reactive protein (CRP) in several aspects:
  • Rises more quickly at onset of inflammation
  • Clears more quickly as inflammation resolves
  • Correlates more closely with sepsis severity
  • Better predicts mortality 3
• In neonatal sepsis specifically, serum PCT levels have been shown to be superior to CRP for:
  • Early diagnosis of neonatal sepsis
  • Detecting the severity of illness
  • Evaluating response to antibiotic treatment 4

Clinical Applications in Infant Sepsis Management

Antibiotic Stewardship

• The Surviving Sepsis Campaign guidelines specifically recommend:
  • PCT levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients (weak recommendation, low quality of evidence) 3
  • PCT levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis but subsequently have limited clinical evidence of infection (weak recommendation, low quality of evidence) 3

Evidence from Clinical Trials

• The NeoPIns trial (2017) demonstrated that PCT-guided decision making was superior to standard care in reducing antibiotic therapy duration in neonates with suspected early-onset sepsis:
  • Reduced antibiotic duration (51.8 vs 64.0 hours in per-protocol analysis)
  • No increase in re-infection or mortality 5

Monitoring Treatment Response

• PCT ratio (day 1 to day 2) following treatment can indicate successful intervention:
  • A ratio higher than 1.14 indicated successful treatment with sensitivity of 83.3% and specificity of 71.4% 3
• Decreasing PCT levels show statistically significant correlation with response to antibiotic treatment, more so than decreasing CRP levels 4

Implementation in Clinical Practice

When to Measure PCT

• At initial presentation with suspected sepsis
• 24-48 hours after initiation of antibiotics to assess response
• When considering discontinuation of antibiotics

Limitations and Caveats

• PCT should not be used alone as a diagnostic marker for neonatal sepsis due to variable specificity 1
• PCT must always be correlated with clinical judgment and other laboratory findings 3
• PCT may have limited value in certain settings:
  • Localized infections
  • Early phase of infection (first 6 hours)
  • Patients already on antibiotics

Algorithm for PCT Use in Infant Sepsis

1. Initial Assessment:

   • Obtain PCT level along with blood cultures and other routine sepsis workup
   • Initiate empiric antibiotics based on clinical presentation, not solely on PCT

2. Interpretation:

   • PCT <0.5 ng/mL: Low likelihood of bacterial sepsis, consider early discontinuation of antibiotics if clinically improving
   • PCT >2.0 ng/mL: High likelihood of bacterial sepsis, continue antibiotics

3. Monitoring:

   • Measure PCT at 24-48 hours after treatment initiation
   • Calculate PCT ratio (day 1:day 2)
   • Ratio >1.14 suggests successful treatment

4. Decision Making:

   • Rapidly declining PCT + clinical improvement + negative cultures = Consider early antibiotic discontinuation
   • Persistent elevation or increasing PCT = Consider treatment failure, source control issues, or alternative diagnoses

In conclusion, while PCT should not be the sole determinant in diagnosing or managing infant sepsis, it provides significant value as part of a comprehensive approach to reduce unnecessary antibiotic exposure while ensuring appropriate treatment for those with true bacterial infections.