Efficacy of linezolid in treatment of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus

The efficacies of orally (p.o. dosed linezolid and intravenously (i.v,) dos ed vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits with experimental aortic-valve endocarditis were investigated. Aft er endocarditis was established with a recent clinical MRSA isolate, rabbit s were dosed for 5 days with linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of body weight or vancomycin (i.v., twice a day) at 25 mg/kg, The 25-mg/kg linezolid group had a high mortality rate and bacterial counts in the valve vegetations that were not different from those of the controls. Linezolid dosed p.o. at 50 and 75 mg/kg and i.v. vancomycin produ ced statistically significant reductions in bacterial counts compared to th ose of the untreated controls: The reduced bacterial counts and culture-neg ative valve rates for the animals treated with linezolid at 75 mg/kg were s imilar to those for the vancomycin-treated animals. Concentrations of linez olid in plasma were determined at several points in the dosing regimen. The se results suggest that the efficacy of linezolid in this infection model i s related to trough levels in plasma that remain above the MIC for this mic roorganism. At the ineffective dose of linezolid (25 mg/kg) the concentrati on at sacrifice was 0.045 times the MIG, whereas the concentrations of line zolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC a t sacrifice, respectively. The results from this experimental model suggest that the oxazolidinone linezolid may be effective for the treatment of ser ious staphylococcal infections when resistance to other antimicrobials is p resent.