Journal Article

Comparison of <i>in vivo</i> intrinsic activity of cefepime and imipenem in a <i>Pseudomonas aeruginosa</i> rabbit endocarditis model: effect of combination with tobramycin simulating human serum pharmacokinetics

Dominique Navas, Jocelyne Caillon, Christele Gras-Le Guen, Cédric Jacqueline, Marie-France Kergueris, Denis Bugnon and Gilles Potel

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 4, pages 767-771
Published in print October 2004 | ISSN: 0305-7453
Published online October 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh381
Comparison of in vivo intrinsic activity of cefepime and imipenem in a Pseudomonas aeruginosa rabbit endocarditis model: effect of combination with tobramycin simulating human serum pharmacokinetics

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Objectives: The purpose of this experimental study was first to compare the in vivo intrinsic activity of imipenem and cefepime administered as a continuous infusion and to determine their lowest effective serum steady-state concentration (LESSC). Secondly, we studied the effect of combining therapy with tobramycin.

Methods: In a Pseudomonas aeruginosa (ATCC 27853) rabbit endocarditis model, β-lactam antibiotics were administered by continuous infusion over a 24 h treatment period at different doses until the LESSC was reached, i.e. able to achieve a 2-log drop of cfu/g of vegetations versus untreated animals. The effect of adding tobramycin (3 mg/kg once daily) was then studied.

Results: The LESSC was between 3× and 4× MIC of cefepime for P. aeruginosa and about 0.25×MIC of imipenem. Combination of tobramycin with each of the two β-lactams did not result in any further significant killing.

Conclusion: The optimal Css/MIC ratio might differ from one molecule to another. The LESSC of imipenem is lower than that of cefepime, giving a better intrinsic activity in vivo, despite a higher MIC in vitro.

Keywords: continuous infusion; lowest effective serum concentration; amimal models

Journal Article.  3580 words. 

Subjects: Medical Oncology ; Critical Care

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