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

Author:

Cirioni Oscar1,Ghiselli Roberto2,Silvestri Carmela1,Kamysz Wojciech3,Orlando Fiorenza4,Mocchegiani Federico2,Di Matteo Fabio2,Riva Alessandra1,Łukasiak Jerzy3,Scalise Giorgio1,Saba Vittorio2,Giacometti Andrea1

Affiliation:

1. Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy

2. Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy

3. Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland

4. Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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