Role of C-Reactive Protein and Procalcitonin in Differentiating Infectious and Non-Infectious Conditions: A Diagnostic Accuracy Study

Background: In general medicine, differentiating between infectious and non-infectious inflammatory causes is one of the biggest diagnostic problems, which results in the wrong use of antimicrobials. Biomarkers commonly used include C-reactive protein (CRP) and procalcitonin (PCT), but their relative and joint applicability remains in need of a more detailed explanation. The objective of the study is to compare and contrast the diagnostic accuracy of CRP versus procalcitonin in distinguishing infectious from non-infectious diseases, and to determine whether combining the two can enhance diagnostic classification. Material and Methods: This study is a cross-sectional diagnostic accuracy study that recruited adult patients with systemic inflammatory features. The final diagnosis of infectious versus non-infectious was made based on microbiological, radiological, and clinical criteria. At presentation, serum CRP and serum PCT were determined. Sensitivity, specificity, positive and negative likelihood ratios, and the diagnostic odds ratio were used to assess diagnostic performance. The Youden index was used to determine optimal cut-off values. Cohen's Kappa was used to test agreement between biomarkers. The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to determine the incremental value of combined biomarkers. The clinical utility was assessed using the decision curve analysis (DCA) based on probability thresholds. Results: Procalcitonin demonstrated greater specificity for infectious disorders, whereas CRP showed higher sensitivity. Integrated CRP-PCT testing demonstrated great improvement in the diagnostic classification (NRI: 0.28, p < 0.01) and net clinical benefit on the decision curve. There was moderate consistency between biomarkers (k = 0.46). Conclusion: CRP and procalcitonin represent complementary results. Their joint use, underpinned by reclassification and decision-analytic techniques, would improve diagnostic quality and potentially encourage more prudent antimicrobial use.

Keywords: CRP, Procalcitonin, Diagnostic Accuracy, Infection, Inflammation.