🧬 Biomarkers to Guide Sepsis Management: The Next Frontier
Abstract: Sepsis remains a leading global cause of mortality and morbidity. This review highlights how biomarkers—from inflammatory mediators to endothelial and immune markers—are increasingly being used to guide key elements of sepsis management: early diagnosis, antibiotic stewardship, fluid therapy, vasopressor initiation, and immunotherapy. Precision therapeutics anchored in biomarker-guided strategies aim to personalize care, improve outcomes, and reduce unnecessary interventions.
Key Insights
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Early Recognition: Heparin-binding protein (HBP), monocyte distribution width (MDW), IL-10, presepsin, procalcitonin (PCT), and CRP show strong predictive value for sepsis onset and progression .
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Bacterial vs. Viral Sepsis: PCT is elevated in bacterial infections, while MxA (Myxovirus resistance protein A) rises in viral sepsis; combined with CRP, they improve diagnostic discrimination .
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Antibiotic Stewardship: PCT remains the most validated marker to guide antibiotic initiation and discontinuation. Trials (e.g., SAPS, PROGRESS) show PCT-guided protocols shorten antibiotic use and reduce mortality .
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Fluid Therapy: Circulating DPP3 and glycocalyx markers (e.g., Syndecan-1) correlate with fluid requirements and outcomes, suggesting potential roles in tailoring resuscitation .
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Vasopressor Guidance: BNP and troponins reflect cardiac strain in septic shock and may inform optimal timing of norepinephrine initiation.
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Immunotherapy: Biomarkers predict response to corticosteroids (CRP >204 mg/L), checkpoint inhibitors (nivolumab), IL-7 (CYT107), and interferon-γ–based therapies.
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COVID-19 Sepsis: Biomarkers such as suPAR and cytokine panels have guided early anakinra use and stratified COVID-19 sepsis phenotypes.
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Clustering Approaches: Machine learning and transcriptomics reveal reproducible sepsis phenotypes (hypo- vs hyperinflammatory, genomic endotypes) that may enable biomarker-driven stratification.
Why This Matters
Sepsis is heterogeneous, and “one-size-fits-all” treatment is failing. This review underscores that biomarker-guided, precision-based therapeutics are not theoretical—they are already shaping antibiotic duration, fluid resuscitation, and immunomodulation.
Conclusion
Biomarkers offer a pathway to individualized sepsis care, from rapid diagnosis to therapy allocation. Implementation challenges remain—cutoff validation, cost, and integration into workflows—but the trajectory toward personalized sepsis management is clear.
Take-Home for Clinicians
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PCT: reliable for antibiotic initiation/cessation.
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HBP, MDW, IL-10: promising for early recognition.
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cDPP3, Syndecan-1: may predict fluid needs and resuscitation risks.
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CRP thresholds: help identify corticosteroid responders.
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Precision sepsis phenotyping is coming—expect machine learning and genomics to integrate into bedside protocols soon.
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