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Invited Commentary
June 2014

Treatment for Necrotizing Soft-Tissue Infections: More Skin in the Game

Author Affiliations
  • 1Department of Surgery, University of Virginia Medical School, Charlottesville
JAMA Surg. 2014;149(6):536. doi:10.1001/jamasurg.2013.4870

The article by Bulger et al1 represents an advance in the world of surgical infections as the first interventional trial using an immunomodulatory agent to treat necrotizing soft-tissue infections. Any prospective interventional study is difficult to execute, and one in such a complicated disease state with such severe morbid effects is even more laudable.

Although the study was small, there were signs of possible improvements during treatment with the novel agent AB103, because the Sequential Organ Failure Assessment scores improved in the active treatment arms compared with the placebo arm at 14 days. There was no significant difference in mortality rates, although this would not be expected given the size of the cohorts. Although the clinical data are impressive, the cytokine data are less convincing. For example, levels of tumor necrosis factor were highest in the group receiving 0.25 mg/kg of AB103 but lowest in the group receiving 0.50 mg/kg. This paradoxical dose-response relationship is not easily explained. It seems either that the baseline characteristics were imbalanced between groups in a way not captured by severity of illness scoring or that cytokines in fact play a minimal role in the pathophysiologic mechanism of this disease. Given the recent publication by Seok et al2 describing poor correlation between murine models and human inflammatory diseases, the latter explanation may be more likely.

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