title: 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.
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Clinica delle Malattie Infettive, c/o Ospedali Riuniti Ancona, Via Conca 71, 60200 Ancona AN, Italy. anconacmi@interfree.it
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Leonardo
authors.initials: L
authors.lastname: Chiodi
authors.forename: Agnese Della
authors.initials: AD
authors.lastname: Vittoria
authors.forename: Vittorio
authors.initials: V
authors.lastname: Saba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D006020:Glycopeptides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D006020:Glycopeptides; D014640:Vancomycin