Comparative pharmacokinetics of ceftazidime in fibrin clots and cardiac vegetations in rabbits with Staphylococcus aureus endocarditis

Abstract

The penetration of ceftazidime, administered in a dose of 100 mg/kg intramuscularly, into cardiac vegetations and subcutaneously implanted fibrin clots was compared in rabbits with experimental Staphylococcus aureus endocarditis. Significant pharmacokinetic differences between the time-concentration curves for the two compartments were observed. Concentrations of ceftazidime in vegetations peaked at 30 min after dosing at a level slightly lower than that in plasma and thereafter declined in parallel with concentrations in plasma throughout the 8-h sampling period. Concentrations in fibrin clots increased more slowly than those in plasma and vegetations, reaching a maximum at 120 min. This was followed by a slow elimination phase yielding concentrations in excess of concurrent plasma and vegetation levels and a greater area under the curve. These features were observed for both large (2-ml volume) and small (0.1-ml volume) clots. Contrary to previous reports, these observations suggest that fibrin clots do not provide an accurate model for predicting antibiotic concentrations in cardiac vegetations produced in endocarditis and that concentrations of antimicrobial agents in vegetations can be predicted more accurately from concomitant plasma levels.