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Experimental study on the efficacy of combination of alpha-helical antimicrobial peptides and vancomycin against Staphylococcus aureus with intermediate resistance to glycopeptides.

Abstract
An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A, two alpha-helical antimicrobial peptides, and vancomycin against Staphylococcus aureus with intermediate resistance to glycopeptides. In vitro experiments included MIC determination, time-kill and synergy studies. For in vivo studies, a mouse model of staphylococcal sepsis has been used. Main outcome measures were: lethality, quantitative blood cultures and detection of TNF-alpha and interleukin-6 (IL-6) plasma levels. Combinations of alpha-helical antimicrobial peptides showed in vitro synergistic interaction. Significant increase in efficacy was also observed in vivo: combined-treated groups had significant lower bacteremia when compared to single-treated groups. Magainin II combined with vancomycin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide future therapeutic alternative in infections due to glycopeptides resistant staphylococci in the coming years.
AuthorsOscar Cirioni, Carmela Silvestri, Roberto Ghiselli, Andrea Giacometti, Fiorenza Orlando, Federico Mocchegiani, Leonardo Chiodi, Agnese Della Vittoria, Vittorio Saba, Giorgio Scalise
JournalPeptides (Peptides) Vol. 27 Issue 11 Pg. 2600-6 (Nov 2006) ISSN: 0196-9781 [Print] United States
PMID16797106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimicrobial Cationic Peptides
  • Glycopeptides
  • Vancomycin
Topics
  • Animals
  • Antimicrobial Cationic Peptides (pharmacology)
  • Disease Models, Animal
  • Drug Resistance, Bacterial
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Glycopeptides (pharmacology)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Protein Structure, Secondary
  • Staphylococcal Infections (drug therapy)
  • Staphylococcus aureus (drug effects)
  • Vancomycin (pharmacology)

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