Diagnostic Accuracy of Presepsin and Its Impact on Early Antibiotic De-Escalation in Burn-Related Sepsis

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a prospective diagnostic accuracy study (January 2021–December 2022; N = 221) in the burn intensive care unit, applying a two-step feature selection to 41 candidate variables. Seven top biomarkers—presepsin, procalcitonin (PCT), albumin, C-reactive protein (CRP), prothrombin time (PT), hematocrit (Hct), and D-dimer—were measured at the moment of clinical sepsis suspicion, concurrently with blood cultures and prior to empirical antibiotic administration, within ±2 h of Sequential Organ Failure Assessment (SOFA). Diagnostic performance was evaluated using a Receiver Operating Characteristic (ROC) curve analysis to determine the area under the curve (AUC), Youden index-derived cut-offs, decision curve analysis, and Net Reclassification Improvement (NRI). Results: Presepsin achieved the highest overall AUC (0.810; 95% CI, 0.742–0.878) and outperformed other markers in culture-negative cases (AUC, 0.846 vs. 0.604; p = 0.015). In the decision curve analysis, presepsin and PCT maintained the largest net benefits at high thresholds, although PT, D-dimer, and Hct also retained smaller positive benefits. Patients were stratified into high- vs. low-risk groups for survival analysis using Youden index cut-offs; Cox regression confirmed PCT (Hazard Ratio 3.78; p < 0.001) and PT (HR 2.12; p = 0.018) as a significant mortality predictor, with presepsin showing borderline significance (HR 3.14; p = 0.055). Conclusions: The high rate of culture-negative sepsis reflects early antibiotic use suppressing culture yield rather than resistance patterns alone. Presepsin’s rapid rise and preserved accuracy under pre-sampling antibiotics suggest its value for early sepsis detection and antimicrobial stewardship. Future work will incorporate polymicrobial and multidrug-resistant bloodstream infection profiles to refine biomarker utility.