To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis.
Prospective, randomized, controlled animal study.
Research laboratory in a university hospital.
Adult male Wistar rats.
Adult male Wistar rats were given an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 lipopolysaccharide or had intraabdominal sepsis induced by cecal ligation and puncture. For each model, all animals were randomized to receive isotonic sodium chloride solution intraperitoneally, 1 mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin combined with 120 mg/kg piperacillin/tazobactam. Each group included 20 animals.
Main outcome measures were: bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin-6, and tumor necrosis factor-α concentrations in plasma; and lethality. All compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with indolicidin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas piperacillin/tazobactam exerted the opposite effect. The combination between indolicidin and piperacillin/tazobactam proved to be the most effective treatment in reducing all variables measured.
Indolicidin may have potential therapeutic usefulness alone and when associated with piperacillin/tazobactam in polymicrobial peritonitis.
From the Department of General Surgery, INRCA-IRRCS, UniversitàPolitecnica delle Marche, Ancona, Italy (RG, FM, FDM, VS); Institute of Infectious Diseases and Public Health, UniversitàPolitecnica delle Marche, Ancona, Italy (AG, OC, CS, AA, GS); and Experimental Animal Models for Aging Units, Research Department, INRCA-IRRCS, Ancona, Italy (FO).
The authors have not disclosed any potential conflicts of interest.
Supported, in part, by Italian Ministry of Education, University, and Research (PRIN 2005).
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