Serum Gasdermin D for Early Diagnosis of Bloodstream Infection and Differentiating Bacterial From Fungal Infections

Abstract

Abstract Background The role of gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown. Methods Serum GSDMD levels were measured in patients with BSI. Endothelial cells and peripheral blood mononuclear cells were isolated and infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence or progression. Results Receiver operating characteristic curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (area under the curve [AUC], .9885). Combining GSDMD with procalcitonin improved the differential diagnosis of gram-positive and gram-negative bacteria (AUC, 0.6699; 66.15% specificity) and early diagnosis of gram-positive bacteria (98.46% sensitivity), while procalcitonin was not significantly elevated. The combined GSDMD and (1-3)-β-D glucan test (G test) had higher sensitivity (AUC, 0.7174) for differential diagnosis of bacterial and fungal infections and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend. Conclusions Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI.