In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus
Cedric Jacqueline, Jocelyne Caillon, Olivier Grossi, Virginie Le Mabecque, Anne-Françoise Miegeville, Denis Bugnon, Eric Batard, Gilles Potel, Cedric Jacqueline, Jocelyne Caillon, Olivier Grossi, Virginie Le Mabecque, Anne-Françoise Miegeville, Denis Bugnon, Eric Batard, Gilles Potel
Abstract
Linezolid in combination with ertapenem showed in vitro synergy against methicillin-resistant Staphylococcus aureus strains. We confirmed this interaction in vivo by using a rabbit endocarditis experimental model and simulation of the human pharmacokinetics in animals for both antibiotics. Linezolid plus ertapenem exhibited highly synergistic activity in vivo after 4 days of treatment.
Figures
Results of dynamic checkerboard method at 24 h for the BCB8 and COL strains. Concentrations of linezolid were as follows: ○, 0; □, one-eighth the MIC; ⋄, one-fourth the MIC; ▵, one-half the MIC; •, 1× the MIC; ▪, 2× the MIC; ⧫, 4× the MIC; ▴, 8× the MIC. Each curve represents a fixed concentration of linezolid combined with different concentrations of ertapenem.
Killing curves for linezolid alone and in combination with ertapenem against BCB8 (solid symbols) and COL (open symbols). Circles, control; diamonds, linezolid at 4× the MIC; squares, ertapenem at 1/128 the MIC; triangles, linezolid at 4× the MIC plus ertapenem at 1/128 the MIC.
Source: PubMed