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Background: Vibrio and Aeromonas species, which can cause necrotizing fasciitis and primary septicemia, are members of the Vibrionaceae family and thrive in aquatic environments. Because the clinical symptoms and signs of necrotizing fasciitis and sepsis caused by these two bacteria are similar, the purposes of this study were to describe the clinical characteristics of Vibrio vulnificus and Aeromonas infections, to analyze the risk factors for death, and to compare the effects of surgical treatment on the outcome.Methods: The cases of thirty-two patients with necrotizing soft-tissue infections and sepsis caused by Vibrio vulnificus (seventeen patients) and Aeromonas species (fifteen patients) were retrospectively reviewed over a four-year period. Surgical débridement or immediate limb amputation was initially performed in all patients. Demographic data, underlying diseases, laboratory results, and clinical outcome were analyzed for each patient in both groups.Results: Six patients in the Vibrio vulnificus group and four patients in the Aeromonas group died. The patients who died had significantly lower serum albumin levels than did the patients who survived (p < 0.05). The patients with a combination of hepatic dysfunction and diabetes mellitus had a higher mortality rate than those with either hepatic disease or diabetes mellitus alone (p < 0.05). The patients with Vibrio vulnificus infections had a significantly lower systolic blood pressure at presentation (p = 0.006). The patients with Aeromonas infections who died had significantly lower white blood-cell counts (p = 0.03) with significantly fewer numbers of segmented white blood cells than those who died in the Vibrio vulnificus group (p = 0.01).Conclusions: The contact history of patients with a rapid onset of cellulitis can alert clinicians to a differential diagnosis of soft-tissue infection with Vibrio vulnificus (contact with seawater or raw seafood) or Aeromonas species (contact with fresh or brackish water, soil, or wood). Early fasciotomy and culture-directed antimicrobial therapy should be aggressively performed in those patients with hypotensive shock, leukopenia, severe hypoalbuminemia, and underlying chronic illness, especially a combination of hepatic dysfunction and diabetes mellitus.Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.