Effect of mono-dose intraperitoneal cecropins in experimental septic shock

Objective: To investigate the efficacy of three cecropins, cecropin A, cecr opin B, and cecropin P1, in preventing lethality in a rat model of septic s hock. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory in a university hospital. Subjects: Adult male Wistar rats. Interventions: Rats were given an intraperitoneal injection of 2 x 10(10) c olony forming units of Escherichia coli, with the exception of the uninfect ed control group (C-0). Animals were randomized to receive, immediately aft er bacterial challenge, intraperitoneally isotonic sodium chloride solution (untreated control group C-1), 1 mg/kg cecropin A (group 2), 1 mg/kg cecro pin B (group 3), 1 mg/kg cecropin P1 (group 4), 20 mg/kg imipenem (group 5) , or 60 mg/kg piperacillin (group 6). Each group included 15 animals. Measurements and Main Results: We measured bacterial growth (quantitative a gar culture) in abdominal exudate and plasma, endotoxin and tumor necrosis factor-alpha concentration in plasma, and mortality. Results were evaluated at 48 hrs after inoculation. Cecropins, piperacillin, and imipenem signifi cantly reduced the lethality and the number of E. coli in abdominal fluid c ompared with saline treatment. In addition, cecropin B significantly decrea sed the lethality compared with piperacillin treatment. Finally, only cecro pins significantly reduced plasma endotoxin concentration. Conclusions. Mono-dose cecropin treatment prevents bacterial growth, endoto xemia, and mortality in rats with septic shock. Cecropin B was the most eff ective compound in reducing all variables measured.