Background: Necrotizing soft tissue infections (NSTI) are fast-progressing infections characterized by severe tissue destruction. These infections are associated with multiorgan failure, septic shock, and high mortality rates. Early diagnosis of these infections is critical but challenging due to vague initial symptoms.
Methods: Through customized Luminex multiplex assays, the concentrations of 36 plasma proteins were measured from 251 NSTI patients and their levels were compared to those in two control groups: 20 non-infected surgical controls and 20 non-NSTI patients, i.e. suspected NSTI but with no necrotic tissue found after surgical examination. The inflammatory response profiles were correlated to clinical parameters and etiology to identify characteristic responses associated with specific clinical endotypes. Statistical analyses comprised univariate Mann-Whitney tests, receiver operating characteristic curves, and random forest models to identify potential biomarkers.
Results: Most protein levels were significantly higher in NSTI patients in comparison to non-infected surgical controls, but only Thrombomodulin was identified as a potential biomarker for NSTI cases in comparison to non-NSTI (AUC 0.95). Moreover, we identified a panel for discrimination of mono- (type II) and poly-microbial (type I) NSTI types conformed by IL-10, CXCL10/IP-10, and MMP9. In addition, a panel consisting of G-CSF, S100A8 and IL-6 was obtained for development of septic shock regardless of the etiology of the infection. All discriminatory biomarkers were confirmed using an additional NSTI validation cohort (n=60).
Conclusion: This study identifies discriminatory biomarkers for early identification of NSTI and its clinical endotypes. These biomarkers are promising candidates for novel diagnostic, prognostic, and therapeutic approaches in NSTI