Comparative pharmacokinetics and pharmacodynamics of amikacin and ceftazidime in tricuspid and aortic vegetations in experimental Pseudomonas endocarditis

Abstract

A factor in the higher medical cure rates for endocarditis in the right as opposed to the left side of the heart in humans may be a difference in antimicrobial pharmacokinetics within vegetations. Rabbits with combined tricuspid and aortic endocarditis due to Pseudomonas aeruginosa received single intravenous doses of either ceftazidime (50 mg/kg) or amikacin (15 or 40 mg/kg). For each antibiotic regimen, areas under the time-concentration curves and percent vegetation penetrances were significantly greater for tricuspid than aortic vegetations (P less than .001). Time-concentration curves for aortic vegetations paralleled those for plasma; curves for the tricuspid vegetations resembled those for subcutaneous fibrin clots. The times above the minimum bactericidal concentration for tricuspid vegetations were significantly longer than those achieved within aortic vegetations for ceftazidime (P less than .01) and amikacin at 15 mg/kg (P less than .001). Antimicrobial pharmacokinetics and pharmacodynamics may be more favorable within tricuspid than aortic vegetations; this difference may, in part, explain more salutary outcomes in bacterial endocarditis involving the right side of the heart.