[Contribution of the experimental model of bacterial endocarditis]

Abstract

Bacterial endocarditis is a difficult to cure infection, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action. The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans, remains of great importance due to the difficulties encountered in clinical trials. The advantage of the experimental model is that besides the fact that is closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens. The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on therapeutic outcome. Two main aspects are discussed for their relevance to human therapy and represent our recent contribution: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis. This animal model has also helped to define the importance of antibiotic dosing strategies to achieve in vivo synergism and to outline the predictive value of some drug pharmacokinetic and dynamic properties on the in vivo response to therapy.