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Antimicrobial Agents and Chemotherapy, December 2008, p. 4351-4355, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00086-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Efficacy of the Combination of Tachyplesin III and Clarithromycin in Rat Models of Escherichia coli Sepsis{triangledown}

Oscar Cirioni,1* Roberto Ghiselli,2 Carmela Silvestri,1 Wojciech Kamysz,3 Fiorenza Orlando,4 Alessandra Riva,1 Elzbieta Kamysz,5 Sefora Castelletti,1 Marco Rocchi,6 Vittorio Saba,2 Giorgio Scalise,1 and Andrea Giacometti1

Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy,1 Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy,2 Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland,3 Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy,4 Faculty of Chemistry, University of Gdansk, Gdansk, Poland,5 Institute of Biomathematics, Faculty of Pharmacy, University of Urbino, Urbino, Italy6

Received 21 January 2008/ Returned for modification 13 April 2008/ Accepted 30 August 2008

We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg Escherichia coli 0111:B4 lipopolysaccharide or (ii) 2 x 1010 CFU of E. coli ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-{alpha}) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-{alpha} concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-{alpha} plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured.

* Corresponding author. Mailing address: Clinica Malattie Infettive, c/o Ospedale Regionale, Via Conca 71, 60020 Torrette AN, Italy. Phone: 39 071 5963715. Fax: 39 071 5963468. E-mail: anconacmi{at}interfree.it

{triangledown} Published ahead of print on 8 September 2008.

Antimicrobial Agents and Chemotherapy, December 2008, p. 4351-4355, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00086-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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