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Alteration of postantibiotic effect during one dosing interval... (1996) Open access

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Title Alteration of postantibiotic effect during one dosing interval of tobramycin, simulated in an in vitro pharmacokinetic model
Published in Antimicrobial Agents and Chemotherapy. ISSN 0066-4804.
Author Hollander, den J.G. (Jan); Mouton, J.W. (Johan); Goor, van M.P.J.; Vleggaar, F.P. (Frank); Verbrugh, H.A. (Henri)
Date 1996-01-01
Language English
Type article
Abstract The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro pharmacokinetic model simulating human pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable.
Publication http://hdl.handle.net/1765/8627
Persistent Identifier urn:NBN:nl:ui:15-1765/8627
Metadata XML
Repository Erasmus University Rotterdam
Erasmus University Rotterdam

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