Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis

Mark S. Rouse, Kerryl E. Piper, Melissa Jacobson, David J. Jacofsky, James M. Steckelberg, Robin Patel

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume57
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Polymethylmethacrylate
  • Rats
  • Vancomycin

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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