In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.
Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.
Jacqueline
Cedric
C
Laboratoire d'Antibiologie (UPRES EA-1156), UER de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.
Asseray
Nathalie
N
Batard
Eric
E
Le Mabecque
Virginie
V
Kergueris
Marie-France
MF
Dube
Laurent
L
Bugnon
Denis
D
Potel
Gilles
G
Caillon
Jocelyne
J
D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005839:Gentamicins / Q000494:pharmacology / Q000627:therapeutic use*; D000069349:Linezolid; D008712:Methicillin / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects*
D000081:Acetamides; D000890:Anti-Infective Agents; D005839:Gentamicins; D023303:Oxazolidinones; D000069349:Linezolid; D008712:Methicillin