Use of an in-vitro kinetic model to study antibiotic combinations

A two compartment pharmacokinetic model was used to study combinations of piperacillin with N-formimidoyl thienamycin or amikacin, and azlocillin with netilmicin against strains of Pseudomonas aeruginosa. Antibiotic antagonism seen with in-vitro static tests of piperacillin and thienamycin did not occur with the kinetic model. Piperacillin plus amikacin showed enhanced activity, and azlocillin prevented bacterial regrowth seen with netilmicin alone during multiple dosing experiments at high bacterial inocula. This model is useful in the study of antibiotic combinations.