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Penetration of daptomycin into bone and synovial fluid in joint replacement
D Montange1, F Berthier2, G Leclerc3
1Laboratoire de Pharmacologie Clinique et Toxicologie, Centre Hospitalier Universitaire de Besançon, Besançon, France EA 3920, Marqueurs Pronostiques et Facteurs de Régulations des Pathologies Cardiaques et Vasculaires-SFR FED 4234, Université de Franche Comté, Besançon, France.
Abstract:
Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.
Insights
Daptomycin effectively penetrates bone tissue, achieving concentrations above the minimum inhibitory concentration for Staphylococcus aureus. This finding supports its use in treating bone and joint infections caused by this pathogen.
Area of Science:
- Pharmacology
- Infectious Diseases
- Orthopedic Surgery
Background:
- Daptomycin is effective against Gram-positive infections, including methicillin-resistant Staphylococcus aureus.
- Limited data exists on daptomycin penetration into bone and synovial fluid.
Purpose of the Study:
- To evaluate daptomycin penetration into bone and synovial fluid following a single intravenous dose.
- To determine if daptomycin concentrations in bone exceed the minimum inhibitory concentration (MIC) for Staphylococcus aureus.
Main Methods:
- A single intravenous dose of 8 mg/kg daptomycin was administered to 16 patients undergoing knee or hip replacement.
- Plasma, bone, and synovial fluid daptomycin concentrations were measured during surgery.
- High-performance liquid chromatography (HPLC) was used for sample analysis.
Main Results:
- Daptomycin bone concentrations were above the MIC for Staphylococcus aureus in all patients.
- Median bone penetration was 9.0% (interquartile range [IQR], 4.4–11.4%).
- Synovial fluid concentrations were also assessed.
Conclusions:
- Daptomycin demonstrates adequate penetration into bone tissue.
- These findings support the clinical use of daptomycin for Staphylococcus aureus bone and joint infections.
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