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. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.