Eileen M. Bulger, Addison May, Andrew Bernard, Stephen Cohn, David C. Evans, Sharon Henry, Jacob Quick, Leslie Kobayashi, Kevin Foster, Therese M. Duane, Robert G. Sawyer, John A. Kellum, Adrian Maung, Greg Maislin, David D. Smith, Irit Segalovich, Wayne Dankner, Anat Shirvan

Necrotizing soft tissue infections (NSTI) represent a rare but devastating disease for which the systemic manifestations have been poorly characterized. In an effort to define an optimal endpoint for clinical trials in this condition, the objective of this study was to establish the pattern of organ dysfunction over time and determine the correlation between organ dysfunction and clinical outcome in patients with NSTI. We conducted a multicenter, retrospective clinical study of patients with NSTI presenting to 12 academic medical centers in the U.S. during 2013. Patients with a diagnosis of NSTI confirmed by surgical findings were included. Organ dysfunction was assessed using a modified Sequential Organ Failure Assessment (SOFA) score (mSOFA: excluding liver) on admission and on hospital days 1, 2, 3, 7, 10, and 14. The presence of organ dysfunction on admission and resolution of organ dysfunction were correlated with clinical parameters, including intensive care unit (ICU)-free days (of 28 d), ventilator-free days, number of debridements, and mortality rate. The incidence of acute kidney injury (AKI) and recovery also were assessed. There were 198 patients enrolled, of whom 62% were male, the mean age was 51 years, and 40% had monomicrobial infections. The mean mSOFA score on admission was 2.4 ± 3.0, with 49% of the patients having a score ≥2 and 35% a score of ≥3. Patients typically demonstrated worsening of the mSOFA score over the first 24 h followed by gradual resolution. An mSOFA ≥3 at admission was associated with a significant decrease in ventilator-free days (mean 20.1 vs. 25.6 days; p < 0.001); ICU-free days (15.2 vs. 23.1, p < 0.001); more debridements (mean 2.3 vs. 2.0; p = 0.11); a higher mortality rate (15.9% vs. 3.1%; p = 0.003); and a higher rate of AKI (59.4 vs. 35.9%; p < 0.001). The persistence of organ dysfunction (mSOFA >1) among survivors at day 14 was associated with fewer ICU-free days (17.8 vs. 23.6; p < 0.001) and ventilator-free days (23.6 vs. 27; p = 0.001) and a lower recovery rate from AKI (38.7% vs. 81.3%; p < 0.001). Early development of systemic organ dysfunction in patients with NSTI is associated with higher morbidity and mortality rates. Failure of the resolution of organ dysfunction by day 14 forecasts a poor outcome. The mSOFA score may be a useful marker for patient selection for inclusion in interventional trials, and the resolution of organ dysfunction by day 14 may be an important clinical endpoint.