Kinetics and bactericidal effect of gentamicin and latamoxef (moxalactam) in experimental Escherichia coli endocarditis.

The pharmacokinetics of gentamicin and latamoxef (moxalactam) were examined in serum, normal heart valves, sterile cardiac vegetations and vegetations infected with Escherichia coli. Penetration of antibiotics into heart valves and vegetations was rapid; the maximum concentration was achieved in both sites at the end of a 20 min iv infusion. However, both antibiotics penetrated better into vegetations than into normal heart valves. In rabbits with left-sided endocarditis, similar antibiotic levels were found in infected vegetations after one or 22 im injections. After 11 im injections (one every 8 h) of latamoxef (15 mg/kg) the bacterial titre (cfu/g) was significantly reduced, but not nil, despite concentrations about 40 times the MBC for this antibiotic in the vegetations. Afer 22 im injections, vegetations in rabbits receiving latamoxef were sterile and were significantly reduced in those receiving gentamicin (1.5 mg/kg/im), concentrations of which in the vegetations were inferior to the MBC. Our results suggest that the in-vivo antibacterial effect depends on local antibiotic levels, kinetics of killing and duration of contact between antibiotic and bacteria.