Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself. 1. Introduction Infection is the most common and most serious complication of major burn injuries and is related to burn size and severity of the injury [1]. Currently, sepsis accounts for 50–60% of deaths in burn patients despite major improvements in antimicrobial therapies. Microbial colonization of the open burn wounds is usually established by the end of the first week after injury [1] despite the use of antimicrobial agents. If the bacterial density overwhelms the immune defenses of the host, invasive burn sepsis may ensue. The burn wound becomes colonized by bacteria in part because of the loss of the skin barrier function, and in part because the burn wound has few or no blood vessels which prevents the antimicrobial action of blood-borne cells from the host immune system. Burn injury leads to suppression of nearly all aspects of the immune response [2]. Postburn serum levels of immunoglobulins, fibronectin, and complement are reduced, and there is a diminished capacity for opsonization of bacteria. Chemotaxis, phagocytosis, and killing functions of neutrophils, monocytes, and macrophages are impaired. Granulocytopenia is common following burn injury. The cellular immune response is impaired, as evidenced by delayed allograft rejection, anergy to common antigens, impaired lymphocyte mitogenesis, and altered mixed lymphocyte responsiveness. Burn injury results in reductions in interleukin-2 (Il-2) production, T-cell and NK cell cytotoxicity, and helper- to- suppressor T-cell ratio (HSR). Clinical findings clearly suggest that burn size profoundly impacts patient immune status and survival of burn patients
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