JAC Advance Access originally published online on December 16, 2005
Journal of Antimicrobial Chemotherapy 2006 57(2):301-305; doi:10.1093/jac/dki435
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Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis
1 Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA; 2 Department of Orthopaedic Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; 3 Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Received 25 August 2005; returned 3 October 2005; revised 26 October 2005; accepted 6 November 2005
* Corresponding author. Tel: +1-507-255-6482; Fax: +1-507-284-9066; E-mail: patel.robin{at}mayo.edu
Background: Infection due to methicillin-resistant Staphylococcus aureus (MRSA) is increasingly common in nosocomial and community settings. Daptomycin is a cyclic lipopeptide anti-infective with activity against MRSA, approved for treatment of complicated skin and skin structure infections. Daptomycin may be useful in systemic or local treatment of chronic osteomyelitis.
Methods: We measured mechanical strength of daptomycin- and vancomycin-loaded polymethylmethacrylate (PMMA), assayed in vivo release of daptomycin and vancomycin from daptomycin- and vancomycin-loaded PMMA, respectively, and compared the efficacy of two systemic doses of daptomycin with that of vancomycin, each with or without the respective anti-infective loaded into PMMA, using a rat model of MRSA chronic osteomyelitis.
Results: Neither tensile nor compressive strength of PMMA was impacted by impregnation with these antimicrobials at a concentration of 7.5% by weight. The peak concentrations of daptomycin and vancomycin in rat tibial bone surrounding a 7.5% daptomycin- and vancomycin-loaded 3 mm PMMA bead were 178 and 49 mg/L, respectively. In the treatment of experimental osteomyelitis, rats assigned to no treatment, daptomycin 50 mg/kg subcutaneously twice daily, daptomycin 60 mg/kg subcutaneously twice daily, and vancomycin 50 mg/kg intraperitoneally twice daily had 6.4, 4.1, 4.0 and 4.5 median log10 cfu/g of bone at the end of 21 days of therapy. All systemic anti-infectives studied were more active than was no treatment. Daptomycin- or vancomycin-loaded PMMA did not, however, exhibit microbiological efficacy alone or adjunctively, as assessed 21 days after implantation.
Conclusions: Daptomycin is released from PMMA in vivo at a rate similar to that of vancomycin. Systemic daptomycin is as active as vancomycin in a rat model of chronic MRSA experimental osteomyelitis.
Keywords: polymethylmethacrylate , rats , vancomycin
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