Efficacy and pharmacodynamics of linezolid, alone and in combination with rifampicin, in an experimental model of methicillin-resistant Staphylococcus aureus endocarditis.
OBJECTIVE
To evaluate the efficacy of oral linezolid, with or without rifampicin, on valve vegetations and secondary foci of infection compared with vancomycin, in the absence or presence of rifampicin, in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.


METHODS
Treatment groups were controls (n = 16), linezolid (n = 15), vancomycin (n = 15), linezolid and rifampicin (n = 15), vancomycin and rifampicin (n = 13), linezolid relapse (n = 11) and vancomycin relapse (n = 9). Therapy lasted 5 days in all groups, with survival of animals in the linezolid relapse and vancomycin relapse groups being recorded for an additional 5 days. Blood was drawn to determine the linezolid concentration, and valve vegetations, and kidney, liver, lung and spleen segments were collected for culture.


RESULTS
Survival in each individual group was higher than that in the control group; 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 except the lung, where only the combination of rifampicin with linezolid was bactericidal.


CONCLUSIONS
Orally administered linezolid is effective in limiting bacterial growth in the secondary foci of endocarditis. Co-administration of rifampicin favoured the suppression of bacterial growth in the lung.
Tsaganos
Thomas
T
4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece. tsag@freemail.gr
Skiadas
Ioannis
I
Koutoukas
Pantelis
P
Adamis
Theodoros
T
Baxevanos
Nikos
N
Tzepi
Ira
I
Pelekanou
Aimilia
A
Giamarellos-Bourboulis
Evangelos J
EJ
Giamarellou
Helen
H
Kanellakopoulou
Kyriaki
K
D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006351:Heart Valves / Q000382:microbiology; D007668:Kidney / Q000382:microbiology; D000069349:Linezolid; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D023421:Models, Animal; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010949:Plasma / Q000737:chemistry; D011817:Rabbits; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D016019:Survival Analysis; D014640:Vancomycin / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid; D012293:Rifampin