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-...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2004-10, Vol.24 (4), p.393-396
Main Authors: Jacqueline, Cedric, Asseray, Nathalie, Batard, Eric, Mabecque, Virginie Le, Kergueris, Marie-France, Dube, Laurent, Bugnon, Denis, Potel, Gilles, Caillon, Jocelyne
Format: Article
Language:English
Subjects:
Acetamides - pharmacology
Acetamides - therapeutic use
Animal models
Animals
Anti-Infective Agents - pharmacology
Anti-Infective Agents - therapeutic use
Antibiotic combinations
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Disease Models, Animal
Drug Resistance, Bacterial
Drug Therapy, Combination - therapeutic use
Endocarditis, Bacterial - drug therapy
Gentamicins - pharmacology
Gentamicins - therapeutic use
Linezolid
Medical sciences
Methicillin - pharmacology
Methicillin - therapeutic use
Microbial Sensitivity Tests
Oxazolidinones
Oxazolidinones - pharmacology
Oxazolidinones - therapeutic use
Pharmacology. Drug treatments
Rabbits
S. aureus
Staphylococcus aureus
Staphylococcus aureus - drug effects
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Summary: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.
ISSN:0924-8579
1872-7913
DOI:10.1016/j.ijantimicag.2004.03.013