Αξιολόγηση της αποτελεσματικότητας της λινεζολίδης, μιας αντισταφυλοκοκκικής οξαζολιδινόνης, σε πειραματικό μοντέλο μικροβιακής ενδοκαρδίτιδας από ανθεκτικό στη μεθικιλλίνη στέλεχος χρυσιζόντος σταφυλόκοκκου (methicillin resistant staphylococcus aureus, MRSA)

Abstract

In order to investigate the in vivo pharmacodynamics of linezolid in an experimental model of aortic-valve endocarditis by methicillin-resistant Staphylococcus aureus and to evaluate the efficacy of linezolid, with or without rifampicin, on both valve vegetations and secondary foci of infection comparative to vancomycin, endocarditis was induced in 81 male rabbits. Treatment groups were: A: controls (n=16); B: linezolid (n=15); C: vancomycin (n=15); D: linezolid and rifampicin (n=15); E: linezolid relapse (n=11); F: vancomycin relapse (n=9). Therapy lasted five days in all groups, with survival of animals in groups E and F being recorded for an additional five days. Blood was drawn for determination of linezolid concentration and valve vegetations and kidney, liver, lung and spleen segments collected for culture. Survival in all groups was prolonged comparative to controls; bacterial load in valve vegetations was reduced by all treatment regimens, with linezolid exhibiting bactericidal effects. Bactericidal activity of linezolid was noted in all secondary foci of infection but lung, where addition of rifampicin was necessary for bactericidal effect. Cmax/MIC ratio of greater than 2.1 and an AUC0>inf/MIC ratio of greater than 2.9 were closely correlated to bactericidal action of linezolid following single dose of the drug. It is concluded that Cmax/MIC and AUC0>inf/MIC ratios are determinant of bacterial eradication following therapy with linezolid; linezolid is also very effective in control of secondary foci. Clinical studies are needed for the implementation of these findings in therapeutics.