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


CONCLUSIONS
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.
Zhang
Shou-Chai
SC
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Zhang
Ling-Ling
LL
Chen
Su-Wan
SW
Wu
Hai-Yan
HY
Liu
Xiao-Kang
XK
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D002443:Ceftriaxone; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam