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PENETRATION OF LINEZOLID INTO OSTE0-ARTICULAR TISSUES

University Department of Orthopaedics, Western Infirmary, Glasgow G11 6NT

Therapy against Methicillin resistant Staphylococcus aureus (MRSA) infection is mainly restricted to the glycopeptide agents (vancomycin and teicoplanin), which require parenteral administration. At present oral antibiotic therapy against MRSA infection is not available. Linezolid is a recently introduced oxazolidinone synthetic antibiotic which acts by inhibiting the initiation of bacterial protein synthesis. It is effective against MRSA, glycopeptide resistant enterococci and all pneumococci irrespective of their penicillin or macrolide resistance. It has excellent oral bioavailability however, there are no data on the penetration of linezolid into osteoarticular tissues. This aim f this study was to measure the concentration of Linezolid in osteoarticular tissues after oral and intravenous administration.

Ten patients undergoing primary total knee replacements for osteoarthritis or rheumatoid arthritis were included in the study. Linezolid was given orally 600mg BD dose for 2 days prior to operation and a final IV 600mg dose 1h before induction on the day of operation. Intra-operatively at 30min after induction, blood, synovial fluid, synovium, muscle and bone samples were collected, processed and assayed for Linezolid concentration. The assay was performed by High Performance Liquid Chromatography (HPLC) method at Antimicrobial Research Laboratory, Westmead Hospital, Bristol.

High concentrations of Linezolid, above the Minimum Inhibitory Concentration (MIC 4) were obtained all sites. Mean (± SD) concentrations for different tis- were: serum 23.0 (6.5) mg/L, synovial fluid 20.1 .4) mg/L, synovium 18.0 (5.6) mg/kg, muscle 18.5 (6.6) bone 8.5 (3.9) mg/kg

Treatment of Methicillin resistant Staphylococcus (MRSA) infections in bone and native or pros- joints is complex and costly. It requires prolonged parenteral and oral antibiotic combination therapy in addition to aggressive surgical debridement. The MICs Linezolid for staphylococci, pneumococci and streptococci are in a range from 0.5 to 2 mg/L whereas MIC enterococci is constant at 4mg/L. A two to six fold increased bioavailability of Linezolid was observed compared to its desired MIC. This study indicates that Linezolid penetrates osteoarticular tissues in sufficient concentration. Linezolid may prove to be an effective or intravenous therapy for serious bone and joint infections with multi-resistant gram-positive bacteria.

Abstracts prepared by Dr P E Watkins, Hodgkin Building, Guys Campus, King’s College London.