Bactericidal activity of simulated serum concentrations of daptomycin vs. vancomycin against vancomycin-susceptible and resistant Enterococcus faecium: a pharmacodynamic model
Abstract number: P1044
Alou L., Aguilar L., Sevillano D., Giménez M.J., Torrico M., González N., Estévez M.J., Prieto J.
Objective: To assess the influence of protein binding (36.9% for vancomycin VAN and 91.7% for daptomycin DAP ) and the decreased susceptibility to VAN in E. faecium on the serum bactericidal activity of VAN and DAP over the dosing interval.
Methods: Serum concentrations after iv 6 mg/kg od DAP vs. 1000 mg bid VAN were simulated in an in vitro computerised one-compartment dynamic model using Mueller Hinton broth supplemented with 4g/dl human albumin and 100 mg/l calcium. Initial inocula: 7.0 log10 cfu/ml. Antibiotic concentrations and colony counts were determined (in triplicate) over 24 h. Pharmacokinetic parameters were determined and AUCall was calculated by the linear-log trapezoidal rule. E. faecium strains (S) were chosen based on VAN MIC/MBC (mg/l): S1(1/32); S2 (2/64) and S3 (128/>128), with DAP MIC/MBC values of 2/16, 2/8 and 4/16 mg/l, respectively.
Results: Cmax (mg/l), t1/2 (h) and AUCs (mg/l x h) were: 44.5 ± 2.6, 6.0 ± 0.5, and 286.5 ± 13.1 for VAN and 85.7 ± 5.8, 8.1 ± 0.2, and 852.7 ± 15.8 for DAP, respectively. Initial inocula ranged from 7.0 to 7.3 log10 cfu/ml. Mean ± SD colony counts (log10 cfu/ml) are shown in the table.
Conclusions: DAP exhibited bactericidal activity (>=3 log10 reduction) at 24 h regardless VAN susceptibility, MBC values or presence of albumin physiological concentrations. VAN was not bactericidal (<1.5 log10 reduction) even against VAN-susceptible strains.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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