Biomarker-Based Differentiation of Gram-Negative and Gram-Positive Bacteremia in Intensive Care Unit Patients

Abstract

Background: Rapid differentiation between gram-negative and gram-positive bacteremia is crucial for optimizing antimicrobial therapy in critically ill patients. This study aimed to evaluate the diagnostic utility of biomarkers, including C-reactive protein (CRP), Interleukin-6 (IL-6), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and leukocyte counts, in distinguishing gram-negative bloodstream infections (BSIs) from gram-positive BSIs, which are more common than gram-positive BSIs in ICU patients. Objectives: The objectives of this study were to evaluate the diagnostic utility of inflammatory biomarkers, including C-reactive protein (CRP), Interleukin- 6 (IL-6), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and leukocyte counts, in differentiating gram-negative and gram-positive bloodstream infections (BSIs) in ICU patients, individually and in combination. Methods: A prospective observational study was conducted on 54 ICU patients aged 18–78 admitted to a university-affiliated hospital between September 2023 and August 2024. Blood culture-confirmed BSIs included 31 gram-negative and 23 cases of gram-positive bacteremia. Biomarkers were measured on the second day of ICU admission to minimize the confounding effects of early interventions. Statistical analyses included the Mann-Whitney U test for group comparisons and the receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance. Results: CRP, sTREM-1, and leukocyte counts were significantly higher in gram-negative bacteremia compared to gram-positive bacteremia (p=0.023, p=0.007, and p=0.017, respectively), while IL-6 showed no significant difference (p=0.407). ROC curve analysis revealed moderate discriminatory power for sTREM-1 (AUC=0.719), leukocyte counts (AUC=0.676), and CRP (AUC=0.646). IL-6 exhibited poor discrimination (AUC = 0.439). A combined biomarker model achieved an improved AUC of 0.782, highlighting the potential of a multi-marker approach. Conclusions: Among the biomarkers studied, sTREM-1 and leukocyte counts demonstrated the highest utility in distinguishing gram-negative from gram- positive bacteremia. The combined use of CRP, IL-6, sTREM-1, and leukocyte counts further enhanced diagnostic accuracy, underscoring the value of a multi-marker strategy in ICU settings. Future studies with larger cohorts are recommended to validate these findings and explore their clinical application.