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Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis

Ghiselli, Roberto PhD, MD; Giacometti, Andrea MD; Cirioni, Oscar PhD, MD; Mocchegiani, Federico PhD, MD; Orlando, Fiorenza PhD; Silvestri, Carmela PhD; Di Matteo, Fabio PhD, MD; Abbruzzetti, Alessandra PhD, MD; Scalise, Giorgio MD; Saba, Vittorio MD

doi: 10.1097/01.CCM.0000292157.60632.89
Laboratory Investigations

Objective: To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis.

Design: Prospective, randomized, controlled animal study.

Setting: Research laboratory in a university hospital.

Subjects: Adult male Wistar rats.

Interventions: 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.

Measurements and Main Results: 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.

Conclusion: 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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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins