Treatment of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis with different doses of teicoplanin

Abstract

Streptococcus viridans continues to be the most frequent causal agent of infective endocarditis. Treatment has become more complicated due to the increase in resistance to penicillin and cephalosporins. In order to study the possible efficacy of teicoplanin at low and high doses, this antibiotic was investigated in rabbits as a monotherapy and in association with gentamicin. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. Infective endocarditis was induced in 120 rabbits with a clinical isolate of Streptococcus sanguis. Treatment was started 48 h after infection, and lasted 5 days. Animals were divided into 6 groups of 20 rabbits each: G1, untreated controls; G2, penicillin+gentamicin; G3 low-dose teicoplanin; G4, low-dose teicoplanin+gentamicin; G5, high-dose teicoplanin; and G6, high-dose teicoplanin+gentamicin. Response to therapy was evaluated with mortality curves, negativization of blood cultures, concentration of S. sanguis in aortic vegetations and rate of sterilization of vegetations. Vegetation weight was significantly lower in treated groups than in controls; lower weights were found in G4, the only treatment that sterilized 65% of vegetations. Death occurred only in the control group (10% mortality). Negativization of blood cultures was greatest and most rapid in G4, followed by G6. Concentrations of S. sanguis in aortic vegetations were significantly lower in all treated groups compared with controls, with the lowest being in groups G4 and G6. Combined treatment with teicoplanin+gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus sanguis. High-dose teicoplanin+gentamicin does not seem to be more efficacious than low-dose teicoplanin+gentamicin.