Bactericidal effect of penicillin, ampicillin, and amoxicillin alone and in combination with tobramycin against...

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.