COMPUTED AMINOGLYCOSIDE CONCENTRATIONS IN ENDOCARDIAL VEGETATIONS - RELATIONS WITH CLINICAL-PRACTICE DURING INFECTIOUS ENDOCARDITIS, EXAMPLE OF AMIKACIN

Using a new computer program SPHERE, amikacine concentrations have bee n computed at various layers of simulated endocardial vegetations. Inp uts are the computed serum (central compartment) concentrations of eit her population pharmacokinetic models or of individualized patient-spe cific models utilizing Bayesian fitting to data of doses given and mea sured serum levels, using the USCPACK PC Clinical Programs. The veget ation is modeled as an isotropic homogeneous sphere. Fick's second law of radial diffusion was applied to compute the in situ antibiotic con centrations. Examination of factors affecting concentrations in vegeta tions shows that in situ peak concentrations are less when the vegetat ion is larger, and when the antibiotic dose, serum concentrations and diffusivity are all less. The results show that early and agressive tr eatment of infectious endocarditis is required with high doses of conc entration-dependent antibiotics, such as aminoglycosides, to achieve t he desired high peak serum levels and to reach effective concentration s deep inside the vegetations.