title: In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time-kill curve methods.
abstract: The in vitro activity of the oxazolidinone linezolid was studied alone and in combination with three antibiotics acting on different cellular targets. Oxazolidinones are bacterial protein synthesis inhibitors that act at a very early stage by preventing the formation of the initiation complex. Combinations of linezolid with gentamicin, vancomycin or rifampicin were evaluated against four methicillin-resistant Staphylococcus aureus strains, using killing curves in conjunction with scanning electron microscopy. Time-kill curves were performed over 24 h using an inoculum of 5 x 10(6)- 1 x 10(7) cfu/mL. Linezolid was studied at concentrations of 1 x, 4 x and 8 x MIC, with partner drugs at 8 x MIC. Addition of linezolid resulted in a decrease of antibacterial activity for gentamicin and vancomycin, and linezolid was antagonistic to the early bactericidal activity of gentamicin. Linezolid, in combination with rifampicin, showed an additive interaction for susceptible strains and inhibited rifampicin-resistant variants. Linezolid plus rifampicin appeared to be the most active combination against methicillin-resistant S. aureus strains in time-kill experiments.
authors.affiliation: Laboratoire d'Antibiologie (UPRES EA-1156), UER de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Jacqueline
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.forename: Virginie
authors.initials: V
authors.lastname: Le Mabecque
authors.forename: Anne-Francoise
authors.initials: AF
authors.lastname: Miegeville
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Donnio
authors.forename: Denis
authors.initials: D
authors.lastname: Bugnon
authors.forename: Gilles
authors.initials: G
authors.lastname: Potel
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D003470:Culture Media; D004338:Drug Combinations; D005839:Gentamicins / Q000494:pharmacology*; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D023303:Oxazolidinones / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D003470:Culture Media; D004338:Drug Combinations; D005839:Gentamicins; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid; D012293:Rifampin