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Linezolid penetration into osteo-articular tissues.

B Rana1, I Butcher, P Grigoris

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The Journal of Antimicrobial Chemotherapy
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Linezolid effectively penetrates bone and joint tissues, achieving concentrations above the minimum inhibitory concentration for common pathogens. This supports its use for treating resistant Gram-positive infections affecting the musculoskeletal system.

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Area of Science:

  • Pharmacokinetics and Drug Penetration
  • Orthopedic Surgery
  • Infectious Diseases

Background:

  • Linezolid is crucial for treating multidrug-resistant Gram-positive infections.
  • Understanding its penetration into osteo-articular sites is vital for effective treatment.
  • Osteo-articular infections require antibiotics with adequate tissue distribution.

Purpose of the Study:

  • To evaluate linezolid penetration into human osteo-articular tissues and fluids.
  • To determine if linezolid concentrations reach levels effective against resistant Gram-positive bacteria in bone and joint.
  • To support the clinical use of linezolid in complex musculoskeletal infections.

Main Methods:

  • A pharmacokinetic study involving 10 patients undergoing total knee replacement.
  • Linezolid administered orally (600 mg q12h) for 48 hours pre-operation, followed by IV dose before anesthesia.
  • High-performance liquid chromatography (HPLC) used to assay linezolid concentrations in serum, synovial fluid, synovium, muscle, and cancellous bone.

Main Results:

  • Mean linezolid concentrations in serum, synovial fluid, synovium, muscle, and cancellous bone were determined.
  • Concentrations achieved were at least double the MIC(90) for staphylococci and streptococci.
  • The antibiotic demonstrated significant penetration into all measured osteo-articular compartments.

Conclusions:

  • Linezolid exhibits excellent penetration into osteo-articular tissues and fluids.
  • Achieved concentrations support the efficacy of linezolid against Gram-positive pathogens in bone and joint infections.
  • These findings validate linezolid's role in managing multidrug-resistant Gram-positive musculoskeletal infections.