COMPUTATION OF DRUG CONCENTRATIONS IN ENDOCARDIAL VEGETATIONS IN PATIENTS DURING ANTIBIOTIC-THERAPY

The treatment of endocarditis often requires prolonged antibiotic ther apy. Individualized drug dosage regimens have made such therapy possib le even in patients with impaired renal function. However, the problem of efficacy remains. Especially for aminoglycosides, it would be a us eful guide to have at least an approximate idea of the concentration o f an antibiotic within an endocardial vegetation. This study was desig ned to develop software to model the drug concentrations at different layers within spherical vegetations to provide a guide during clinical therapy of patients with endocarditis. A general model describing the diffusion of antibiotics in spheres has now been developed and interf aced with the USCPACK PC Clinical Programs in order to compute and pl ot concentrations, within the vegetation, based on the regimen given t o the patient and the diffusitivity of the antibiotic into the vegetat ion. Some preliminary results of this research, which are still in pro gress, are presented. Diffusion into simulated spherical vegetations h as been computed for different treatment regimens for endocarditis: am ikacin or netilmicin and vancomycin were given to three elderly patien ts (3 women, 74, 75 and 92 years old, with initial estimated creatinin e clearances of 51, 36, and 31 ml/min/1.73 m(2), respectively). Althou gh Amikacin has a low diffusivity, the concentrations, even in the cen ter of the vegetation, appear to be effective. The effects of various regimens, including a 'once-a-day' aminoglycoside regimen, are present ed.