JAC Advance Access published online on March 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg160
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Laboratoire d'Antibiologie
(UPRES EA-1156), UER de Médecine, 1 rue Gaston Veil, 44035
Nantes Cedex 01
* Corresponding author. E-mail: gpotel{at}sante.univ-nantes.fr.
Received 25 October 2002
; revised 8 November 2002
; 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
In vitro activity of linezolid
alone and in combination with gentamicin, vancomycin or rifampicin
against methicillin-resistant Staphylococcus aureus by
time-kill curve methods
2 Laboratoire
de Bactériologie, Hôpital Pontchaillou, Rennes,
France
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