[Aminoglycoside determinations calculated in endocarditis vegetations. Relations with clinical practices during infectious endocarditis treatment with amikacin]. / Concentrations calculées en aminoside dans des végétations d'endocardites. Relations avec les pratiques cliniques lors du traitement d'endocardites infectieuses par l'amikacine.

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.

Intravegetation antimicrobial distribution in endocarditis: a numerical model and establishment of the conditions for an in-vitro test.

Two problems appear when it is desired to get good knowledge concerning transfer of matter through a material, and especially the penetration of antibiotics into vegetations on heart valves. One is to build a numerical model to describe and simulate the process and thus to gain a fuller insight into the nature of the transfer. The other is to develop an in vitro test to represent the in vivo process, with simple operational conditions and accurate measurements. The in vitro test must enable one to measure the parameters of interest, i.e. the diffusivity of antibiotic through the vegetation, or rather through the blood located in the vegetation. Experiments and calculations are made in order to build a numerical model describing the process and to develop an in vitro test capable of determining the diffusivity. A simulation is made with a polymer bead made of Ethylene vinyl acetate saturated by a liquid such as n-heptane with a slight amount of benzene. The release of benzene from the polymer bead into n-heptane free from benzene is the best way for measuring the diffusivity of the benzene (simulating the antibiotic) through the liquid located in the polymer.