Pharmacokinetic and pharmacodynamic requirements for antibiotic therapy of experimental endocarditis.

Bacterial endocarditis is a deep, difficult-to-cure infection. Although most organisms are highly susceptible to many antibiotics, therapy must be maintained for weeks in order to eradicate the infection. Moreover, recent clinical observations with teicoplanin have reemphasized that treatment failure can occur, even with very susceptible organisms, after conventional durations of therapy (35). The difficulty encountered in sterilizing vegetations is usually explained by (i) the poor penetration of antibiotics into infected vegetations, (ii) the altered metabolic state of the organisms within the vegetation, and (iii) the absence of a host defense cellular response inside the vegetation which could cooperate with the antibiotic action. All three explanations were evoked very early in the antibiotic era, and after 50 years of antibiotic use, it is still difficult to distinguish between myth and reality. In this minireview we analyze what experimental models of endocarditis have taught us about (i) the pharmacokinetics of antibiotic permeation of fibrin vegetations and (ii) the specificity of pharmacodynamics in vegetations. We also describe the clinical consequences of these two parameters on the antibiotic dosing regimen and the length of therapy.