Antiendotoxin activity of antimicrobial peptides and glycopeptides

An animal study was performed to investigate the efficacy of two glycopeptides and two cationic peptides in the prevention of lethality in a septic shock rat model. Adult Wistar rats were given an intraperitoneal injection of 2x10(10) CFU of Escherichia coli ATCC 25922, with the exception of an uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (control group C1), 3 mg/Kg teicoplanin (group 1), 7 mg/Kg vancomycin (group 2), 1 mg/Kg colistin (group 3), 1 mg/Kg buforin II (group 4), or 60 mg/Kg piperacillin (group C(PIP)). In addition, four groups (1a, 2a, 3a, and 4a) received the above mentioned drugs in combination with piperacillin. All compounds and combinations significantly reduced the lethality and the number of E. coli in abdominal fluid compared with C1 group, with the exception of the glycopeptides. Colistin and buforin II combined with piperacillin significantly decreased the lethality compared with piperacillin alone. Finally, colistin, buforin II, and teicoplanin significantly reduced plasma endotoxin concentration in comparison with piperacillin and saline treatment. Antimicrobial peptides and teicoplanin act as antiendotoxin agents and enhance the efficacy of piperacillin.