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

Abstract

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-alpha 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.

• Authors: Roberto Ghiselli, Andrea Giacometti, Oscar Cirioni, Federico Mocchegiani, Fiorenza Orlando, Carmela Silvestri, Fabio Di Matteo, Alessandra Abbruzzetti, Giorgio Scalise, Vittorio Saba
• Journal: Critical care medicine (Crit Care Med) Vol. 36 Issue 1 Pg. 240-5 (Jan 2008) ISSN: 1530-0293 [Electronic] United States
• PMID: 18090372 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides
• indolicidin
• Penicillanic Acid
• Tazobactam
• Piperacillin

Topics

• Animals
• Anti-Infective Agents (therapeutic use)
• Antimicrobial Cationic Peptides (therapeutic use)
• Disease Models, Animal
• Drug Therapy, Combination
• Enterococcus faecalis (drug effects)
• Escherichia coli (drug effects)
• Escherichia coli Infections (drug therapy, microbiology)
• Gram-Positive Bacterial Infections (drug therapy, microbiology)
• Male
• Microbial Sensitivity Tests
• Penicillanic Acid (analogs & derivatives, therapeutic use)
• Peritonitis (drug therapy)
• Piperacillin (therapeutic use)
• Rats
• Rats, Wistar
• Shock, Septic (drug therapy)
• Tazobactam
• Treatment Outcome