Diagnostic utility of sepsis screening tools, procalcitonin, and C-reactive protein in nosocomial fever of unknown origin

Abstract

BACKGROUND

Nosocomial fever of unknown origin (nFUO) is a frequent and challenging diagnostic entity, encompassing diverse infectious and non-infectious etiologies. Timely identification is crucial, yet evidence on the diagnostic accuracy of commonly employed sepsis screening tools and biomarkers remains sparse. We hypothesized that these tools and biomarkers measured at fever onset could distinguish infectious from non-infectious causes of nFUO in critically ill adults.

AIM

To evaluate the diagnostic utility of sepsis tools and biomarkers in identifying infectious causes of nFUO.

METHODS

This prospective observational study included patients admitted to the Acute Care Emergency Medicine Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India (July 2023 to December 2024). nFUO was defined by Durack and Street criteria. Diagnostic performance of sepsis screening tools (systemic inflammatory response syndrome, Sequential Organ Failure Assessment, quick Sequential Organ Failure Assessment, National Early Warning Score, and Modified Early Warning Score) and biomarkers [procalcitonin (PCT), C-reactive protein (CRP)] at fever onset was assessed using receiver operating characteristic curve analysis.

RESULTS

Of 80 cases (mean age 42.9 ± 16.5 years; 80% male), 42.5% had infectious causes, 38.7% non-infectious, and 18.8% remained undiagnosed. Pneumonia (26.2%) and bloodstream infections (11.2%) were the most common infectious etiologies, while central fever and thrombophlebitis (each 7.5%) were predominant among non-infectious causes. Sepsis tools showed poor diagnostic accuracy, with area under the receiver operating characteristic curve (AUC) values close to 0.5. PCT demonstrated modest performance (AUC = 0.61; optimal cut-off: 0.85 μg/L), while CRP was paradoxically higher in non-infectious cases (AUC = 0.45). Overall mortality was 20% and was highest among undiagnosed patients (33.3%). Fever duration and hospitalization length were significantly greater in infectious cases.

CONCLUSION

Sepsis tools, PCT, and CRP have limited utility in identifying infectious causes of nFUO in critically ill adults and should not solely guide initial decision-making.

Keywords: Critical care; Fever of unknown origin; Nosocomial; Sepsis; Screening tools; Procalcitonin; C-reactive protein

Core Tip: Nosocomial fever of unknown origin is a frequent and complex challenge in critically ill patients, requiring prompt differentiation between infectious and non-infectious causes. This study evaluates the diagnostic performance of sepsis screening tools, procalcitonin, and C-reactive protein at fever onset. Findings reveal limited utility of all sepsis tools. Procalcitonin shows modest accuracy, while C-reactive protein is unreliable. Given the associated high mortality, this study emphasizes the importance of a structured, systematic evaluation over empirical antibiotic use, and highlights the need for advanced diagnostic modalities to improve infection detection.