Saini S, Pahil S, Mohindra R, Sachdeva N, Sharma N, Pannu AK. Diagnostic utility of sepsis screening tools, procalcitonin, and C-reactive protein in nosocomial fever of unknown origin. World J Crit Care Med 2025; 14(3): 106496 [DOI: 10.5492/wjccm.v14.i3.106496]
Corresponding Author of This Article
Ashok K Pannu, MD, Additional Professor, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, 4th Floor, F Block, Chandigarh 160012, India. gawaribacchi@gmail.com
Research Domain of This Article
Critical Care Medicine
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Shashikant Saini, Ritin Mohindra, Navneet Sharma, Ashok K Pannu, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Sapna Pahil, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Naresh Sachdeva, Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Author contributions: Saini S, Pahil S, Mohindra R, Sachdeva N, and Sharma N collected data; Pannu AK designed the research study and analyzed the data; Saini S, Pahil S, Mohindra R, Sachdeva N, Sharma N, and Pannu AK wrote the manuscript; and all authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Postgraduate Institute of Medical Education and Research, approval No. INT/IEC/2023/SPL-1250.
Informed consent statement: All study participants, or legally acceptable representatives, provided informed written consent before study enrollment.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ashok K Pannu, MD, Additional Professor, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, 4th Floor, F Block, Chandigarh 160012, India. gawaribacchi@gmail.com
Received: March 3, 2025 Revised: April 11, 2025 Accepted: May 7, 2025 Published online: September 9, 2025 Processing time: 141 Days and 10.4 Hours
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.
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.
