https://www.selleckchem.com/products/GDC-0449.html Necrotizing soft tissue infections (NSTI) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation and aggressive surgical management has significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. We performed a combined analysis of NSTI patients from the ACCUTE randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) in order to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified SOFA (mSOFA) score ≥2 at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA <1. The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA ≤1 had significantly lower 90-day mortality than those with mSOFA ≥2 in both ATB-202 (2.4% vs 21.5%; p<0.001) and ATB-204 (6% vs 16% p=0.008) studies. Additionally, in an adjusted covariate analysis of the combined study datasets D14 mSOFA ≤1 was an independent predictor of lower 90-day mortality (OR 0.26, 95% CI 0.13-0.53; p=0.001). In both studies, D14 mSOFA ≤1 was associated with more favorable discharge status and decreased resource utilization. For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. Prognostic/epidemiology study, Level III. Prognostic/epi