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Antimicrobial Agents and Chemotherapy, June 2007, p. 2005-2010, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01576-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Efficacy of Tachyplesin III, Colistin, and Imipenem against a Multiresistant Pseudomonas aeruginosa Strain{triangledown}

Oscar Cirioni,1* Roberto Ghiselli,2 Carmela Silvestri,1 Wojciech Kamysz,3 Fiorenza Orlando,4 Federico Mocchegiani,2 Fabio Di Matteo,2 Alessandra Riva,1 Jerzy Lukasiak,3 Giorgio Scalise,1 Vittorio Saba,2 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, Italy4

Received 19 December 2006/ Returned for modification 12 January 2007/ Accepted 23 March 2007

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.

* Corresponding author. Mailing address: Clinica delle Malattie Infettive, c/o Ospedali Riuniti Ancona, Via Conca 71, 60200 Ancona, AN, Italy. Phone: 39 071 5963715. Fax: 39 071 5963468. E-mail: o.cirioni{at}univpm.it

{triangledown} Published ahead of print on 2 April 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 2005-2010, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01576-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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