title: Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Department of Surgery, University of Washington , Seattle, Washington.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.affiliation: 2 Department of Surgery, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Addison
authors.initials: A
authors.lastname: May
authors.affiliation: 3 Department of Surgery, University of Kentucky Healthcare , Lexington, Kentucky.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bernard
authors.affiliation: 4 Department of Surgery, The University of Texas Health Sciences at San Antonio , San Antonio, Texas.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cohn
authors.affiliation: 5 Department of Surgery, The Ohio State University , Columbus, Ohio.
authors.forename: David C
authors.initials: DC
authors.lastname: Evans
authors.affiliation: 6 Department of Surgery, University of Maryland , Baltimore, Maryland.
authors.forename: Sharon
authors.initials: S
authors.lastname: Henry
authors.affiliation: 7 Department of Surgery, University of Missouri , Columbia, Missouri.
authors.forename: Jacob
authors.initials: J
authors.lastname: Quick
authors.affiliation: 8 Department of Surgery, University of California , San Diego, California.
authors.forename: Leslie
authors.initials: L
authors.lastname: Kobayashi
authors.affiliation: 9 Department of Surgery, Maricopa Integrated Health Systems , Phoenix, Arizona.
authors.forename: Kevin
authors.initials: K
authors.lastname: Foster
authors.affiliation: 10 Department of Surgery, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Duane
authors.affiliation: 11 Department of Surgery, University of Virginia , Charlottesville, Virginia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sawyer
authors.affiliation: 12 Department of Critical Care, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: 13 Department of Surgery, Yale University , New Haven, Connecticut.
authors.forename: Adrian
authors.initials: A
authors.lastname: Maung
authors.affiliation: 14 Biomedical Statistical Consulting , [city], Pennsylvania.
authors.forename: Greg
authors.initials: G
authors.lastname: Maislin
authors.affiliation: 15 Department of &&&City of Hope, Duarte, California.
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.affiliation: 16 AtoxBio Ltd. , Ness Ziona Israel .
authors.forename: Irit
authors.initials: I
authors.lastname: Segalovich
authors.affiliation: 16 AtoxBio Ltd. , Ness Ziona Israel .
authors.forename: Wayne
authors.initials: W
authors.lastname: Dankner
authors.affiliation: 16 AtoxBio Ltd. , Ness Ziona Israel .
authors.forename: Anat
authors.initials: A
authors.lastname: Shirvan
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology* / Q000401:mortality; D009336:Necrosis / Q000150:complications*; D063305:Organ Dysfunction Scores; D011379:Prognosis; D012189:Retrospective Studies; D018461:Soft Tissue Infections / Q000150:complications*; D016019:Survival Analysis; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult