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, beta-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 x and 4 x MIC of cefepime for P. aeruginosa and about 0.2 5x MIC of imipenem. Combination of tobramycin with each of the two beta-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.
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) rabbitendocarditis model, beta-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 x and 4 x MIC of cefepime for P. aeruginosa and about 0.2 5x MIC of imipenem. Combination of tobramycin with each of the two beta-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.
Authors: Brad Moriyama; Stacey A Henning; Richard Childs; Steven M Holland; Victoria L Anderson; John C Morris; Wyndham H Wilson; George L Drusano; Thomas J Walsh Journal: Ann Pharmacother Date: 2010-04-06 Impact factor: 3.154
Authors: Paul Skorup; Lisa Maudsdotter; Miklós Lipcsey; Markus Castegren; Anders Larsson; Ann-Beth Jonsson; Jan Sjölin Journal: PLoS One Date: 2014-02-28 Impact factor: 3.240
Authors: J Mensa; J Barberán; A Soriano; P Llinares; F Marco; R Cantón; G Bou; J González Del Castillo; E Maseda; J R Azanza; J Pasquau; C García-Vidal; J M Reguera; D Sousa; J Gómez; M Montejo; M Borges; A Torres; F Alvarez-Lerma; M Salavert; R Zaragoza; A Oliver Journal: Rev Esp Quimioter Date: 2018-02-23 Impact factor: 1.553