In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus

International Journal of Antimicrobial Agents
Cedric JacquelineJocelyne Caillon

Abstract

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.

Citations

Mar 10, 2006·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·E E HillW E Peetermans
Jun 12, 2013·Current Infectious Disease Reports·Cédric JacquelineDavid Boutoille
Jan 29, 2005·The Journal of Biological Chemistry·Yuxin ChenRobert S Hodges
Jul 13, 2012·Infection and Drug Resistance·Sally Ager, Kate Gould
May 20, 2006·Scandinavian Journal of Infectious Diseases·Nathalie GodonChristele Gras-Le Guen
Mar 4, 2009·Enfermedades infecciosas y microbiología clínica·Francisco GudiolUNKNOWN Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
Jan 19, 2007·International Journal of Antimicrobial Agents·Eleni MylonaNikolaos Chatzis
Nov 4, 2015·Antimicrobial Agents and Chemotherapy·A del RíoUNKNOWN Hospital Clinic Experimental Endocarditis Study Group
Jun 16, 2019·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Kayla M Galanter, Jackie Ho

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