[Aminoglycoside determinations calculated in endocarditis vegetations. Relations with clinical practices during...

Using a new computer program SPHERE, amikacin concentrations have been computed at various layers of simulated endocardial vegetations. Inputs are the computed serum (central compartment) concentrations of either population pharmacokinetic models or of individualized patient-specific models utilizing Bayesian fitting to data of doses given and measured serum levels, using the USC*PACK PC Clinical Programs. The vegetation is modeled as an isotropic homogeneous sphere. Fick's second law of radial diffusion was applied to compute the in situ antibiotic concentrations. Examination of factors affecting concentrations in vegetations shows that in situ peak concentrations are less when the vegetation is larger, and when the antibiotic dose, serum concentrations and diffusivity are all less. The results show that early and aggressive treatment of infectious endocarditis is required with high doses of concentration-dependent antibiotics, such as aminoglycosides, to achieve the desired high peak serum levels and to reach effective concentrations deep inside the vegetations.