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- Title
Therapeutic efficacy of the magainin analogue MSI-78 in different intra-abdominal sepsis rat models.
- Authors
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
- 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 × 1010 cfu 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.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2004, Vol 54, Issue 3, p654
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkh390