[Post antibiotic, post beta-lactamase inhibitor and post antibiotic sub-MIC effect of ceftriaxone/tazobactam on beta-lactamase-producing Escherichia coli in vitro].

Sichuan Da Xue Xue Bao Yi Xue Ban

Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.

Published: November 2009

Objective: To study post antibiotic effect (PAE), post beta-lactamase inhibitor effect (PLIE) and post antibiotic sub-MIC effect (PASME) of ceftriaxone/tazobactam on beta-lactamase-producing Escherichia coli in vitro.

Methods: The minimal inhibitory concentration (MIC) of ceftriaxone/tazobactam against 4 types of beta-lactamase producing E. coli strains, was measured by two-fold agar dilution method. The numbers of CFU on plates were counted by micro-inoculation colony counting method. The growth kinetics curves of the bacteria were drawn according to CFU counts, from which the PAE, PLIE and PASME were calculated.

Results: The MIC of the ceftriaxone/tazobactam combination was eight times more than ceftriaxone alone. No longer PAE (-0.59-0.85 h) was found in the ceftriaxone/tazobactam combination or any of them alone. The PLIE and PASME varied according to the type of beta-lactamase but similar results were observed for the strains producing the same type beta-lactamase. All PLIEs (0.62-3.22 h) and most PASMEs (0.12-5.61 h) were longer than PAEs. The lower MIC of ceftriaxone the strain had, the longer the PAE, PLIE and PAMSE were.

Conclusion: The duration of PLIE and PASME may concerned with the type of beta-lactamase. With both longer PLIE and PASME, longer dosing interval should be recommended. The PAE, PLIE and PASME provide an important instrument for pharmacodynamic studies of antibiotics, in particular for the design of dosing schedules.

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