INFLUENCE OF PROTEIN-BINDING ON THE PHARMACODYNAMICS OF CEFTAZIDIME OR CEFTRIAXONE AGAINST GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA IN AN IN-VITRO INFECTION MODEL

The antibacterial activity of ceftriaxone and ceftazidime against Gram -positive and Gram-negative bacteria, clinically isolated from patient s hospitalized in intensive care unit, was compared in vitro. The stud y was performed using a dynamic model in which the human kinetics of t he drugs after i.m. administration were simulated. The antibacterial a ctivity was tested by determining viable colony forming units (CFU) of bacteria/ml. Kill curves were constructed by plotting the log CFU/ml versus time. Simultaneously with CFU detection, ceftriaxone and ceftaz idime concentrations were assayed by HPLC. The results obtained show t hat ceftriaxone and ceftazidime exert the same killing activity agains t the highly sensitive strains tested. Against the less sensitive stra ins, both drugs have initial good killing activity followed by bacteri al regrowth using ceftriaxone while no regrowth was observed using cef tazidime. These data indicate that both ceftazidime and ceftriaxone ex hibit primarily time-dependent bacterial killing. Moreover, only unbou nd drug appears to be effective, so only free drug should be considere d in the pharmacokinetic-pharmacodynamic interaction.