Activity of serum concentrations of daptomycin vs. vancomycin against vancomycin-susceptible and resistant Enterococcus faecium in the presence of albumin physiological concentrations: an in vitro pharmacodynamic simulation
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Killing curves with daptomycin (56 μg/ml, the Cmax after 4 mg/kg) in media containing albumin physiological concentrations showed bactericidal activity against Enterococcus faecium, but due to its high protein binding (91.7%), cidal activity was delayed when compared to that in media without albumin . This study explores the activity over 24 h of simulated serum concentrations of daptomycin (after 6 mg/kg od regimen) vs. vancomycin (1,000 mg bid regimen) against two vancomycin-susceptible but tolerant and one resistant E. faecium in an in vitro pharmacodynamic device using media containing albumin physiological concentrations. A one-compartment dynamic model was used to expose bacteria to changing study drug concentrations  using Mueller Hinton broth supplemented with albumin (4 g/dl). In daptomycin simulations, media was calcium-adjusted by adding 100 μg/ml of Ca2+ . Albumin concentrations were determined by the bromcresol green method, ionized calcium concentrations were...
KeywordsVancomycin Daptomycin Initial Inoculum Bromcresol Bromcresol Green
To N. González for her technical assistance and J. Prieto for his critical review of the manuscript.
This study was supported by an unrestricted grant from Novartis Farmacéutica S.A., Barcelona, Spain.
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