Can presepsin be used as a biomarker for Community-Acquired Pneumonia (CAP)?

Can Presepsin Be Used as a Biomarker for Community-Acquired Pneumonia?

Presepsin can be used as a biomarker for CAP, particularly for assessing disease severity and predicting mortality, but it is not recommended by current guidelines for routine diagnostic or treatment decisions.

Current Guideline Position

The major CAP guidelines from the American Thoracic Society and Infectious Diseases Society of America do not mention presepsin as a recommended biomarker 1. These guidelines focus primarily on procalcitonin (PCT) as the inflammatory biomarker with the most evidence, though even PCT should not be used alone to guide antibiotic decisions 1, 2, 3. The 2023 Taiwan guidelines for COVID-19-associated infections similarly emphasize PCT and C-reactive protein but do not include presepsin in their recommendations 1.

Research Evidence Supporting Presepsin Use

Despite the absence of guideline recommendations, research demonstrates that presepsin has clinical utility in specific CAP contexts:

Diagnostic Performance

• Presepsin shows superior diagnostic accuracy for severe CAP compared to PCT, with an area under the curve (AUC) of 0.867 for predicting 30-day mortality versus 0.728 for PCT 4
• In ICU patients with severe CAP, presepsin demonstrated better diagnostic capability than PCT for identifying community-acquired pneumonia among patients admitted for acute respiratory failure 5
• Presepsin levels correlate with bacterial etiology and can distinguish bacterial from viral pneumonia 6, 7

Prognostic Value

• Presepsin levels >754 pg/mL are associated with significantly increased 30-day mortality (hazard ratio of 19.472) in hospitalized CAP patients 4
• Combining presepsin with the Pneumonia Severity Index (PSI) improves mortality prediction (AUC = 0.892) compared to either marker alone 4
• Elevated admission presepsin levels predict adverse short-term outcomes including ICU admission and 30-day mortality 6
• Presepsin predicts ICU mortality in both sepsis and severe CAP patients 5

Severity Stratification

• Presepsin levels are significantly elevated in high-risk CAP patients (PSI >130) compared to low or moderate-risk groups 4
• Non-survivors have significantly higher plasma presepsin levels than survivors: 1083 pg/mL versus 385 pg/mL 4
• Presepsin distinguishes between severe sepsis and septic shock in CAP patients 5

Practical Clinical Application

For severity assessment and prognostic stratification:

• Measure presepsin at hospital admission in patients with confirmed CAP requiring hospitalization 4, 5
• Use a cutoff of >754 pg/mL to identify patients at high risk for 30-day mortality 4
• Combine presepsin measurement with PSI score for optimal mortality prediction 4
• Consider presepsin particularly useful in ICU patients with severe CAP where distinguishing bacterial from other etiologies is challenging 5

For diagnostic purposes:

• Presepsin may help differentiate severe CAP from other causes of acute respiratory failure in ICU settings 5
• Presepsin correlates with bacterial etiology but should not replace comprehensive microbiologic workup 6, 7

Important Limitations and Caveats

Presepsin is not a standalone diagnostic tool and cannot replace clinical judgment, radiographic confirmation, or microbiologic testing 1. The major CAP guidelines emphasize that biomarkers should supplement, not replace, comprehensive clinical assessment 1, 2.

Presepsin has not been validated for antibiotic stewardship decisions in the way that PCT has been studied 1, 2, 3. While PCT can guide antibiotic duration in CAP (though this remains controversial), no similar evidence exists for presepsin 1, 3.

The evidence base for presepsin remains limited to observational studies 6, 4, 5. Unlike PCT, which has been evaluated in multiple randomized controlled trials for antibiotic stewardship, presepsin lacks this level of evidence 1, 3.

Presepsin is most valuable in severe CAP and ICU settings rather than outpatient or mild-to-moderate CAP 4, 5. The guidelines recommend minimal diagnostic testing for outpatients with CAP 1.

Comparison to Established Biomarkers

Presepsin appears to outperform PCT for mortality prediction in CAP (AUC 0.867 vs 0.728) 4, and shows better diagnostic accuracy than PCT for severe CAP in ICU patients 5. However, PCT remains the only biomarker with guideline support for potential use in antibiotic stewardship, albeit with significant caveats 1, 2, 3.

C-reactive protein, while mentioned in guidelines, has limited specificity for bacterial infection and is not recommended for routine use in CAP diagnosis 1, 7. Presepsin demonstrates more specificity for bacterial infection than traditional inflammatory markers 7.

Clinical Bottom Line

Use presepsin selectively for prognostic stratification in hospitalized CAP patients, particularly those with severe disease or in ICU settings, but do not use it to guide initial antibiotic decisions or as a replacement for clinical assessment and microbiologic testing. The strongest evidence supports combining presepsin with PSI score to identify patients at highest risk for mortality who may benefit from more aggressive monitoring and management 4.