What serum markers are used to detect sepsis?

Serum Markers of Sepsis

For sepsis detection, measure procalcitonin (PCT) and C-reactive protein (CRP) when the probability of bacterial infection is low to intermediate, but do not rely on these biomarkers alone when infection probability is high or in established septic shock. 1

Primary Biomarkers: PCT and CRP

The 2023 Society of Critical Care Medicine guidelines provide clear direction on biomarker use 1:

Procalcitonin (PCT)

• Rises within 4 hours of bacterial exposure, peaks at 6-8 hours
• Normal values: <0.05 ng/mL
• Use when infection probability is low-to-intermediate to guide clinical evaluation
• Do NOT use to rule out infection when probability is already high 1
• Results available within 1 hour with point-of-care testing
• Important caveat: Recent data show PCT can be elevated in severe viral illness (influenza, COVID-19), reducing its discriminatory power 1

C-Reactive Protein (CRP)

• Rises 12-24 hours after inflammatory insult, peaks at 48 hours
• Normal values: <5 mg/L; typical cutoff: 10 mg/L
• Same recommendation as PCT: use in low-to-intermediate probability scenarios 1
• Affected by neutropenia, immunodeficiency, and NSAIDs 1
• Available within minutes to 1 hour

The guidelines do not favor one over the other when choosing between PCT and CRP 1. Both serve primarily to assist in antimicrobial discontinuation rather than initial diagnosis.

Lactate: The Critical Resuscitation Marker

Lactate ≥4 mmol/L defines septic shock and lactate ≥2 mmol/L with persistent hypotension requiring vasopressors also indicates shock 2. The 2016 Surviving Sepsis Campaign guidelines recommend:

• Normalize lactate as a resuscitation target in patients with elevated levels 2
• Lactate serves as a marker of tissue hypoperfusion, not just infection severity

Guideline Position on Routine Biomarker Use

Critical distinction: The guidelines recommend AGAINST routine biomarker use in established sepsis and septic shock due to uncertain benefit, cost, and availability issues 1. Biomarkers have a role primarily when:

1. Fever is present with lower likelihood of infection
2. Obtaining baseline values to guide antibiotic discontinuation
3. Clinical assessment is equivocal

Emerging and Research Biomarkers

While not yet guideline-endorsed, recent high-quality research identifies promising markers:

IL1R2 (Interleukin-1 Receptor Type 2)

• Superior diagnostic performance (AUC = 0.908) compared to PCT and CRP 3
• Rises within 4 hours, peaks at 24 hours post-sepsis
• Correlates with SOFA scores and predicts 28-day mortality 3
• Not yet available for routine clinical use

Other Investigated Markers

• IL-6, IL-8, IL-10: Significantly elevated in sepsis vs. SIRS 4
• Urokinase, ICAM-1: Combined AUC of 0.741 for sepsis diagnosis 4
• CD64: AUC 0.88 for sepsis, 0.95 for bacterial infection (cutoff: 45-46 abc) 5
• sPLA2-IIA: Excellent performance (AUC 0.93 for sepsis, 0.97 for bacterial infection) 5

Clinical Algorithm for Biomarker Use

Step 1: Assess clinical probability of bacterial infection

• High probability (clear focus, shock, obvious infection): Do NOT wait for PCT/CRP; start antibiotics immediately 1, 2
• Low-to-intermediate probability: Measure PCT and/or CRP to guide decision-making 1

Step 2: Measure lactate in all suspected sepsis cases

• If ≥2 mmol/L with hypotension: Assume septic shock, initiate aggressive resuscitation 2
• Target lactate normalization during resuscitation 2

Step 3: Use biomarkers for antimicrobial stewardship

• Obtain baseline PCT/CRP to guide discontinuation of antibiotics 1
• Serial measurements more valuable than single values

Common Pitfalls

1. Do not delay antibiotics waiting for biomarker results in septic shock—antibiotics must be given within 1 hour 2
2. PCT can be falsely elevated in severe viral infections 1
3. CRP is nonspecific and affected by multiple factors 1
4. Band cell percentage shows good correlation with mortality but is less accurate than PCT 6
5. In post-cardiac surgery patients with prolonged cardiopulmonary bypass, clinical parameters (fever, hypotension, tachycardia, elevated lactate) outperform laboratory markers for early detection 7

Special Populations

• Hematologic malignancies: IL-6, PCT, and monocytes show strong predictive value (AUC >0.75) 8
• Solid tumors: Biomarker performance is limited; PCT shows only moderate elevation (AUC 0.693) 8
• Post-cardiac surgery: Clinical signs more reliable than laboratory markers in first 3-5 days 7