Efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain

Antimicrob Agents Chemother. 2007 Jun;51(6):2005-10. doi: 10.1128/AAC.01576-06. Epub 2007 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use
  • Colistin / administration & dosage
  • Colistin / pharmacology*
  • Colistin / therapeutic use
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / pharmacology*
  • DNA-Binding Proteins / therapeutic use
  • Drug Resistance, Multiple, Bacterial*
  • Drug Therapy, Combination
  • Humans
  • Imipenem / administration & dosage
  • Imipenem / pharmacology*
  • Imipenem / therapeutic use
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests / methods
  • Microbial Sensitivity Tests / standards
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / therapeutic use
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • DNA-Binding Proteins
  • Peptides, Cyclic
  • tachyplesin peptide, Tachypleus tridentatus
  • Imipenem
  • Colistin