Influence of protein binding on the pharmacodynamics of ceftazidime or ceftriaxone against gram-positive and gram-negative bacteria in an in vitro infection model

Journal of Chemotherapy
F ScaglioneF Fraschini

Abstract

The antibacterial activity of ceftriaxone and ceftazidime against Gram-positive and Gram-negative bacteria, clinically isolated from patients hospitalized in intensive care unit, was compared in vitro. The study was performed using a dynamic model in which the human kinetics of the drugs after i.m. administration were simulated. The antibacterial activity 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 ceftazidime concentrations were assayed by HPLC. The results obtained show that ceftriaxone and ceftazidime exert the same killing activity against the highly sensitive strains tested. Against the less sensitive strains, both drugs have initial good killing activity followed by bacterial regrowth using ceftriaxone while no regrowth was observed using ceftazidime. These data indicate that both ceftazidime and ceftriaxone exhibit primarily time-dependent bacterial killing. Moreover, only unbound drug appears to be effective, so only free drug should be considered in the pharmacokinetic-pharmacodynamic interaction.

References

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Citations

Sep 10, 2008·Antimicrobial Agents and Chemotherapy·Stephan SchmidtHartmut Derendorf
Sep 28, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Oliver GhobrialJeffrey D Hillman
Nov 20, 1998·Journal of Chemotherapy·I M Gould
Sep 18, 2004·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·I Gustafsson, O Cars

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