S-thanatin in vitro prevents colistin resistance and improves its efficacy in an animal model of Pseudomonas aeruginosa sepsis.

Abstract

An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.

• Authors: Oscar Cirioni, Guoqiu Wu, Linxian Li, Fiorenza Orlando, Carmela Silvestri, Roberto Ghiselli, Zilong Shen, Eleonora Gabrielli, Lucia Brescini, Giovanni Lezoche, Mauro Provinciali, Mario Guerrieri, Andrea Giacometti
• Journal: Peptides (Peptides) Vol. 32 Issue 4 Pg. 697-701 (Apr 2011) ISSN: 1873-5169 [Electronic] United States
• PMID: 21262298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• thanatin
• Colistin

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Antimicrobial Cationic Peptides (therapeutic use)
• Colistin (pharmacology)
• Disease Models, Animal
• Drug Resistance, Microbial
• Male
• Mice
• Mice, Inbred BALB C
• Microbial Sensitivity Tests
• Pseudomonas Infections (drug therapy, microbiology)
• Pseudomonas aeruginosa (isolation & purification)
• Sepsis (drug therapy, microbiology)