Antibacterial activity and kill kinetics of amoxicillin-clavulanic acid combinations against Escherichia coli and Klebsiella aerogenes.

Combinations of amoxicillin and clavulanic acid were tested against 11 Escherichia coli strains and five Klebsiella aerogenes strains. Apart from one E. coli, the strains were highly resistant to amoxicillin due to beta-lactamase production. Synergy was demonstrated in all strains by agar dilution. Synergy was detected against the beta-lactamase-producing strains under simulated in vivo conditions with constantly decreasing concentrations simulating in vivo pharmacokinetics. The correlation between antibacterial activity determined by minimum inhibitory concentrations and bacterial kill kinetics in the in vivo simulation model was acceptable. A higher bacterial kill rate was observed when the antibiotic dosage was increased beyond the minimum concentration where an antibacterial effect was seen; this was not demonstrable by traditional agar dilution tests. In combination, a greater relative amount of amoxicillin compared to clavulanic acid allows a reduction in the total amount of antimicrobial agents with the same degree of antibacterial activity.