JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 857-864
© 2003 The British Society for Antimicrobial Chemotherapy
In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time–kill curve methods
1 Laboratoire d’Antibiologie (UPRES EA-1156), UER de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 01; 2 Laboratoire de Bactériologie, Hôpital Pontchaillou, Rennes, France
Received 25 October 2002; returned 8 November 2002; revised 14 January 2003; accepted 20 January 2003
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 106– 1 x 107 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.
Keywords: oxazolidinones, in vitro susceptibility study, drug combination interactions
* Corresponding author. Tel/Fax: +33-240-41-2854; E-mail: gpotel{at}sante.univ-nantes.fr
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