Therapeutic efficacy of the magainin analogue MSI-78 in different intra-abdominal sepsis rat models

Andrea Giacometti, Roberto Ghiselli, Oscar Cirioni, Federico Mocchegiani, Giuseppina D'Amato, Fiorenza Orlando, Valerio Sisti, Wojciech Kamysz, Carmela Silvestri, Piotr Naldoski, Jerzy Łukasiak, Vittorio Saba, Giorgio Scalise

Research output: Contribution to journalArticle

Abstract

Objectives: This study was designed to investigate the antimicrobial and anti-endotoxin activity of MSI-78, a synthetic cationic peptide analogue of magainin 2. Methods: The in vitro antimicrobial activity of MSI-78 was investigated against the commercially available quality control strain Escherichia coli ATCC 25922. In addition, three rat models of septic shock were investigated: (i) rats were injected intraperitoneally with 1 mg Escherichia coli 0111:B4 LPS; (ii) rats were given an intraperitoneal injection of 2 × 1010cfu of Escherichia coli ATCC 25922; (iii) intra-abdominal sepsis was induced via caecal ligation and puncture. All animals were randomized to receive after 360 min intravenously isotonic sodium chloride solution, 1 mg/kg MSI-78, or 60 mg/kg piperacillin. Main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumour necrosis factor α (TNF-α) concentrations, and lethality. Results: Our in vitro data showed that MSI-78 possesses a strong activity against Escherichia coli. The in vivo studies showed that all compounds reduced the lethality when compared to controls. MSI-78 showed a slightly higher antimicrobial activity than piperacillin and achieved a substantial decrease in endotoxin and TNF-α plasma concentrations than the β-lactam. Conclusions: Because of its strong double anti-endotoxin and antimicrobial activities MSI-78 could be an interesting compound for Gram-negative septic shock treatment.

Original languageEnglish
Pages (from-to)654-660
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume54
Issue number3
DOIs
Publication statusPublished - Sep 2004

Keywords

  • Endotoxin
  • Peptides
  • Septic shock

ASJC Scopus subject areas

  • Microbiology
  • Pharmacology

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    Giacometti, A., Ghiselli, R., Cirioni, O., Mocchegiani, F., D'Amato, G., Orlando, F., Sisti, V., Kamysz, W., Silvestri, C., Naldoski, P., Łukasiak, J., Saba, V., & Scalise, G. (2004). Therapeutic efficacy of the magainin analogue MSI-78 in different intra-abdominal sepsis rat models. Journal of Antimicrobial Chemotherapy, 54(3), 654-660. https://doi.org/10.1093/jac/dkh390