Kinetic in vitro Studies of Antibacterial Effects of the Combination of New Penicillins and Cefalosporins against Proteus vulgaris

In vitro studies simulating human as well as animal pharmacokinetics were performed in order to assess the combination effect of mezlocillin plus cefotaxime or cefoperazone. Different Proteus vulgaris strains exhibiting varying degrees of in vivo response to the antibiotics were selected for this study. Retardation of bactericidal efficacy was caused by the combination of mezlocillin plus cefoperazone in those strains exhibiting high degrees of beta-lactamase inducibility and being exposed to high levels of cefoperazone; lower drug levels caused indifferent effects. In any case, cultures were completely sterilized during the study period. Among the three beta-lactams studied, cefoperazone was the best beta-lactase inducer, while cefotaxime and mezlocillin exhibited only minor inducer activity. The combination of mezlocillin with cefotaxime, being only minimally active as beta-lactamase inducers, caused either indifferent or synergistic effects when simulating drug disposition in humans or animals. beta-Lactamase-negative strains exhibited only indifferent effects. The augmented bioavailability of mezlocillin due to its simultaneous administration with a cefalosporin resulted in an increased antibacterial efficacy.