Therapeutic efficacy of intraperitoneal polymyxin B and polymyxin-like peptides alone or combined with levofloxacin in rat models of septic shock

The efficacy of two polymyxin-like peptides, KFFKFFKFF and IKFLKFLKFL, alone and combined with levofloxacin, was investigated in a rat model of septic shock. Rats were given an ip injection of 2 x 10(10) cfu of Escherichia coli and randomized to receive ip isotonic sodium chloride solution, 7 mg/kg levofloxacin, 1 mg/kg polymyxin B and 1 mg/kg of each polymyxin-like peptides alone or combined with 7 mg/kg levofloxacin. Polymyxins achieved a significant reduction in plasma endotoxin and tumour necrosis factor alpha (TNF-alpha) concentration. Levofloxacin significantly reduced the bacterial growth and TNF-alpha concentration. The combinations of polymyxin-like peptides and levofloxacin demonstrated the highest efficacy.