Inhibitory activity and bactericidal kinetics of mecillinam/ampicillin combinations against Enterobacteriaceae, Pseudomonas and Acinetobacter

Mecillinam, ampicillin and combinations of the two were tested against Enterobacteriaceae by traditional agar dilution and under in vitro conditions simulating in vivo pharmacokinetics. Synergy was demonstrated by agar dilution in 30% of the strains. At simulated in vivo conditions, synergy between ampicillin and mecillinam was detected in a high osmolality medium, but not when the osmolality of the medium was low. The bactericidal effect was detected with mecillinam after one hour, while that of ampicillin or the combination was detected after 15 min. Changed bacterial morphology was observed by electron microscopy. Mecillinam produced ovoid spherical cell structures whereas combinations of the two drugs produced larger bacterial spheres.