How can presepsin be used as an early biomarker for detecting sepsis in children presenting with signs of infection or systemic inflammatory response?

Presepsin as an Early Biomarker for Pediatric Sepsis

Presepsin shows promise as an early diagnostic biomarker for pediatric sepsis, but current evidence does not support its routine use in clinical practice, as the 2020 Surviving Sepsis Campaign pediatric guidelines do not recommend any specific biomarker for sepsis diagnosis or risk stratification. 1

Current Guideline Recommendations

The most authoritative guidance comes from the 2020 Surviving Sepsis Campaign International Guidelines for pediatric septic shock and sepsis-associated organ dysfunction. These guidelines notably do not recommend presepsin or any specific biomarker for sepsis diagnosis. Instead, they emphasize:

• Systematic screening for timely recognition of septic shock and sepsis-associated organ dysfunction in acutely unwell children (weak recommendation) 1
• Blood cultures before antimicrobials when this doesn't substantially delay treatment 1
• No recommendation could be issued regarding blood lactate values for risk stratification 1

The guidelines prioritize clinical recognition and rapid treatment over biomarker-driven diagnosis, recommending antimicrobial therapy within 1 hour for septic shock and within 3 hours for sepsis-associated organ dysfunction without shock 1.

Research Evidence on Presepsin Performance

While guidelines don't endorse presepsin, recent research provides insights into its potential utility:

Diagnostic Accuracy

The most recent high-quality study (2024) found presepsin levels significantly differed between viral (309 pg/mL) and bacterial infections (526 pg/mL, p=0.0398), with confirmed sepsis cases showing markedly elevated levels (3328 pg/mL). 2 This suggests presepsin may help distinguish bacterial from viral etiologies—a clinically valuable distinction.

However, diagnostic performance varies considerably across studies:

• Sensitivity ranges from 72-100% depending on cutoff values 3, 4
• Optimal cutoffs vary widely from 447 pg/mL to 970 ng/L across different populations 3, 5, 6, 7
• A 2023 systematic review found the highest sensitivity-specificity ratio at 94% vs 100% using a cutoff of 855 ng/L 3

Critical Limitations

Presepsin has significant limitations that prevent routine clinical adoption:

• Poor early diagnostic ability: A 2026 study found presepsin had low diagnostic accuracy (AUC 0.62) in early neonatal sepsis, inferior to CRP (AUC 0.77) 7
• Limited prognostic value: A 2022 study showed presepsin lacks diagnostic ability early in disease and has limited prognostic potential for predicting mortality 8
• Better for severity than diagnosis: Presepsin appears more useful for assessing sepsis severity (particularly in shock) than for initial diagnosis 8

When Presepsin May Be Most Useful

The evidence suggests presepsin performs best in specific scenarios:

1. Distinguishing bacterial from viral infections in febrile children presenting to emergency departments 2
2. Identifying gram-negative infections when measured on day 3 (cutoff ≥970 ng/L) 6
3. Assessing severity in established sepsis, particularly when combined with procalcitonin 8, 5
4. Ruling out sepsis when combined with procalcitonin: one 2026 study found 100% NPV when both biomarkers were in low-risk ranges 9

Practical Clinical Approach

Given the absence of guideline support and variable research evidence, presepsin should NOT replace clinical judgment or delay treatment in suspected pediatric sepsis. If available, consider the following algorithm:

For Emergency Department Evaluation:

1. Prioritize clinical assessment using systematic screening tools
2. Obtain blood cultures before antibiotics (if no significant delay)
3. If presepsin is available, interpret cautiously:
   • Values >2000 pg/mL suggest confirmed sepsis 2
   • Values >640-970 ng/L warrant high suspicion 3, 6
   • Low presepsin AND low procalcitonin may help rule out sepsis 9
4. Never delay antimicrobials waiting for presepsin results

Common Pitfalls to Avoid:

• Don't use presepsin alone for diagnosis—it lacks sufficient sensitivity/specificity
• Don't rely on presepsin in the first 24 hours—it performs poorly for early diagnosis 8, 7
• Don't use universal cutoffs—optimal values vary by age, population, and clinical context
• Don't substitute presepsin for clinical judgment—guidelines emphasize rapid empiric treatment based on clinical recognition, not biomarkers

Comparison with Established Biomarkers:

Presepsin shows mixed performance compared to traditional markers:

• Versus CRP: One study found presepsin inferior (AUC 0.62 vs 0.77) 7
• Versus Procalcitonin: Combined use may improve diagnostic accuracy 9
• Versus soluble Mannose Receptor: sMR showed superior performance (AUC 1.0,100% sensitivity/specificity) 5

In summary, while presepsin shows biological plausibility and some promising research findings, the lack of guideline endorsement, variable cutoff values, poor early diagnostic performance, and limited prognostic utility mean it cannot currently be recommended for routine clinical use in pediatric sepsis recognition. Clinical assessment, rapid treatment initiation, and blood cultures remain the standard of care 1.