Assessment of TIMP1, Transgelin-2, and Procalcitonin as Protein Biomarkers for Diagnosis and Prognosis of Bloodstream Infection in a Critically Ill Cohort

BACKGROUND: Bloodstream infections (BSI) are a significant contributor to morbidity and mortality among hospitalized patients. Rapid diagnosis of BSI is critical for timely and appropriate clinical management, but current diagnostic strategies have a prolonged turnaround time or only identify select pathogens with minimal prognostic information. METHODS: We examined serial serologic samples from 77 intensive care unit (ICU) patients at time points before, during, and after diagnosis of presumptive BSI to identify host-derived protein biomarkers associated with specific organisms and with clinical outcomes in BSI. ICU patients with and without BSI were included. Two candidate biomarkers, tissue metalloproteinase 1 (TIMP-1) and transgelin-2 (transgelin), were analyzed using enzyme-linked immunosorbent assay (ELISA) analysis and with procalcitonin (PCT) as a positive control. RESULTS: TIMP-1 was higher in those with gram-negative BSI [median = 746 ng/mL, interquartile range (IQR): 355-1410] than gram-positive BSI (662 ng/mL, 396-1111), and culture negative (377 ng/mL, 189-708). For transgelin, those with gram-negative BSI were highest (14.6 ng/mL, 9.6-22.0), followed by gram-positive BSI (9 ng/mL, 6.1-16), and negative cultures (9.1 ng/mL, 5.6-13.0). PCT was highest among patients with gram-positive BSI (10.8 ng/mL, 1.3-23.3), followed by gram-negative BSI (7.7 ng/mL, 1.6-57.7), and negative cultures (1.2 ng/mL, 0.3-3.5). The multiplicative product of all 3 markers had an AUC of 0.8 (0.7-0.9). No biomarker was associated with risk for ICU admission, 30-day mortality, or length of stay. CONCLUSION: TIMP1 and transgelin-2 are candidate biomarkers for diagnosing BSI. Larger studies comparing their utility to PCT and other sepsis biomarkers are warranted.