Antibacterial activity and kill kinetics of ampicillin/sulbactam (CP-45899) combinations against Escherichia coli and Klebsiella aerogenes.

Combinations of ampicillin and sulbactam (CP-45899) were tested against 11 strains of Escherichia coli and five strains of Klebsiella aerogenes. With the exception of one E. coli, strain, the strains were all highly resistant to ampicillin. Synergy was demonstrated by agar dilution in six of the ten resistant E. coli strains and in three of the five K. aerogenes strains. At simulated in vivo conditions with constantly decreasing concentrations mimicking in vivo pharmacokinetics, synergy was detected against the beta-lactamase-producing strains tested, although the activity against the more resistant K. aerogenes strains was low. The correlation between antibacterial activity as determined by minimum inhibitory concentrations and the bacterial kill kinetics exhibited in the in vivo simulation model was acceptable for E. coli. The relationship was less predictable for K. aerogenes, however.