Comparative evaluation of daptomycin (LY146032) and vancomycin in the treatment of experimental methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits

Abstract

A rabbit model for methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis was used to compare treatment with daptomycin, a new peptolide, and vancomycin. Daptomycin (4 mg/kg) and vancomycin (40 mg/kg) were injected subcutaneously every 12 and 6 h, respectively. After treatment, MRSA was found in bone cultures from 18 of 18 control rabbits, 10 of 17 animals treated with daptomycin, and 11 of 18 animals treated with vancomycin. Drug concentrations were measured in serum, uninfected bone, and infected bone 1 h after daptomycin or vancomycin was injected in a group of rabbits that had been infected for 3 to 4 weeks. Vancomycin was present at the highest concentrations in infected and uninfected bone. The results of this study suggest that daptomycin was similar to vancomycin in the eradication of MRSA from infected bone in an experimental model of osteomyelitis.

Emergence of a Clinical Daptomycin-Resistant Staphylococcus aureus Isolate during Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Osteomyelitis

“…Bone cultures remained positive in 59% of the animals after 28 days of daptomycin treatment, and the daptomycin levels in infected bone were 1.3% of those found in serum (8). The study modeled a divided daptomycin dosing regimen, which was pharmacodynamically suboptimal for this concentration-dependent bactericidal agent (2,8,15). Similar to our patient, Rezai and colleagues (K. Rezai et al, Abstr.…”

“…Information on the utility of daptomycin for treatment of osteomyelitis is limited. A rabbit model of MRSA osteomyelitis demonstrated the similar efficacies of daptomycin and vancomycin (8). Bone cultures remained positive in 59% of the animals after 28 days of daptomycin treatment, and the daptomycin levels in infected bone were 1.3% of those found in serum (8).…”

“…A rabbit model of MRSA osteomyelitis demonstrated the similar efficacies of daptomycin and vancomycin (8). Bone cultures remained positive in 59% of the animals after 28 days of daptomycin treatment, and the daptomycin levels in infected bone were 1.3% of those found in serum (8). The study modeled a divided daptomycin dosing regimen, which was pharmacodynamically suboptimal for this concentration-dependent bactericidal agent (2,8,15).…”

Development of Daptomycin Resistance In Vivo in Methicillin-Resistant Staphylococcus aureus

“…In an experimental rabbit model, Mader and Adams demonstrated similar microbiologic eradications of MRSA from infected tibias of animals treated with vancomycin or daptomycin at comparable peak plasma levels but a poorer radiologic response to daptomycin. In that study, daptomycin concentrations in infected bone were lower than vancomycin concentrations and no daptomycin could be measured in healthy bone (4). Failure to debride patient 2's infection may also have contributed to relapse.…”

Clinical Progression of Methicillin-Resistant Staphylococcus aureus Vertebral Osteomyelitis Associated with Reduced Susceptibility to Daptomycin

“…In an experimental rabbit model of MRSA tibial osteomyelitis, 41% of daptomycin-and 39% of vancomycin-treated rabbits had negative tibial cultures for MRSA after 28 days of therapy (8). Compared to daptomycin, vancomycin was present in significantly higher levels in both infected and uninfected bone; daptomycin was not detectable in uninfected bone.…”