Bactericidal effect of penicillin, ampicillin, and amoxicillin alone and in combination with tobramycin against Enterococcus faecalis as determined by kill-kinetic studies

Abstract

Fifteen strains of Enterococcus faecalis, all clinical blood culture isolates from patients with endocarditis, were studied by kill-kinetic experiments using penicillin G, ampicillin and amoxicillin alone and in combination with tobramycin. The median minimal inhibitory concentrations (MIC), were penicillin 4 mg/l, ampicillin 2 mg/l, amoxicillin 2 mg/l and tobramycin 32 mg/l. Equipotent doses of the antibiotics (1/2 x MIC, 1 x MIC and 4 x MIC) were used in the kill-kinetic studies. Synergism was studied using a combination of 1/2 x MIC of the beta-lactam antibiotic and 8 mg/l of tobramycin. The bactericidal activity did not exceed 10(+3) cfu/ml at 5 hours for any single compound. After 5 h all three beta-lactam antibiotics in combination with tobramycin resulted in synergism, i.e. more than one hundredfold reduction of colony forming units (cfu) as compared to the most active single agent. Amoxicillin had a significantly higher bactericidal potential than ampicillin or penicillin both alone and in combination with tobramycin. The clinical significance of these findings warrants further studies in vivo.