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JAC Advance Access originally published online on August 4, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(3):654-660; doi:10.1093/jac/dkh390
JAC vol.54 no.3 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

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

Andrea Giacometti1,*, Roberto Ghiselli2, Oscar Cirioni1, Federico Mocchegiani2, Giuseppina D'Amato1, Fiorenza Orlando3, Valerio Sisti1, Wojciech Kamysz4, Carmela Silvestri2, Piotr Naldoski4, Jerzy Lukasiak4, Vittorio Saba2 and Giorgio Scalise1

1 Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona; 2 Department of General Surgery, I.N.R.C.A.—I.R.R.C.S., Università Politecnica delle Marche, Ancona; 3 Biotechnology Centre, Research Department, I.N.R.C.A.—I.R.R.C.S., Ancona, Italy; 4 Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland

* Corresponding author. Present address. Clinica delle Malattie Infettive, c/o Ospedale Regionale, Via Conca, 71, 60020 Torrette AN, Italy. Tel: +39-071-5963715; Fax: +39-071-5963468; Email: anconacmi{at}interfree.it

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 x 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 {alpha} (TNF-{alpha}) 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-{alpha} plasma concentrations than the ß-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.

Keywords: septic shock , endotoxin , peptides


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 Innate ImmunityHome page
J. Andra, T. Gutsmann, P. Garidel, and K. Brandenburg
Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds
Innate Immunity, October 1, 2006; 12(5): 261 - 277.
[Abstract] [PDF]


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