Contribution of animal models in the search for effective therapy for endocarditis due to enterococci with high-level resistance to gentamicin

Abstract

Earlier studies suggest that ampicillin and amoxicillin are more effective than other beta-lactam agents in killing enterococci, although beta-lactam agents are slowly and incompletely bactericidal against most strains of Enterococcus faecalis. We previously showed that continuous infusion of ampicillin is more effective than intermittent administration in decreasing the number of enterococci in valvular vegetations of rats with catheter-induced endocarditis that are treated for 5 days. In this model, we found ampicillin plus sulbactam more effective than ampicillin alone against a beta-lactamase-producing enterococcal strain with high-level resistance to gentamicin. Daptomycin therapy produced results approximately equal to those of ampicillin plus sulbactam. Vancomycin and teicoplanin given for 5 days at doses producing equivalent serum levels had approximately equal efficacy. However, 10-day therapy with low-dose teicoplanin was considerably more effective than similar treatment with vancomycin. High-dose teicoplanin for 5 days produced sterile valves in 82% of the animals studied.