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Antimicrobial Agents and Chemotherapy, January 2002, p. 101-104, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.101-104.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Single-Dose Intraperitoneal Magainins Improve Survival in a Gram-Negative-Pathogen Septic Shock Rat Model

Oscar Cirioni,1,2* Andrea Giacometti,1 Roberto Ghiselli,2 Federico Mocchegiani,2 Anna Fineo,1 Fiorenza Orlando,3 Maria Simona Del Prete,1 Marco Rocchi,4 Vittorio Saba,2 and Giorgio Scalise1

Institute of Infectious Diseases and Public Health, University of Ancona,2 Department of General Surgery 1,2 Biotechnology Centre, Research Department, INRCA IRRCS, University of Ancona, Ancona,3 Institute of Biomathematics, Faculty of Pharmacy, University of Urbino, Urbino, Italy4

Received 2 July 2001/ Returned for modification 15 August 2001/ Accepted 5 October 2001

The therapeutic efficacies of three polycationic peptides selected among the class of the magainins (magainin I, magainin II, and magainin II amide), alone and combined with piperacillin, were investigated in a rat model of septic shock. Rats were given an intraperitoneal injection of 2 x 1010 CFU of Escherichia coli and randomized to receive intraperitoneally isotonic sodium chloride solution, 60 mg of piperacillin per kg of body weight, and 1 mg of each magainin per kg alone and combined with 60 mg of piperacillin per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-{alpha}) concentrations in plasma, and lethality. Treatments with the magainins achieved significant reductions of bacterial growth and plasma endotoxin and TNF-{alpha} concentrations. In general, treatments with the combinations of magainins and piperacillin demonstrated the highest efficacies.

* Corresponding author. Mailing address: Clinica delle Malattie Infettive, c/o Ospedale Regionale, via Conca, 60020 Ancona, Italy. Phone: 39 071 5963715. Fax: 39 071 5963468. E-mail: anconacmi{at}interfree.it.

Antimicrobial Agents and Chemotherapy, January 2002, p. 101-104, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.101-104.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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