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Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 29 - 29
1 Dec 2015
Seaton R Sarma J Malizos K Militz M Menichetti F Riccio G Jeannot G Trostmann U Pathan R Hamed K
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Of the 6075 patients enrolled in EU-CORE registry, 206 patients had orthopaedic device-related infections. Significant underlying diseases were reported in 71% patients, most frequently cardiovascular disease (38%). The common sites of infection were knee (40%) and hip (33%). Among the 170 patients with available culture results, 135 (79%) were positive. Coagulase-negative staphylococci (CoNS, 44%) and Staphylococcus aureus (43%, of those 47% were methicillin resistant) were the most commonly isolated pathogens. Daptomycin was used empirically in 48% patients and as second-line therapy in 67% patients. During daptomycin therapy, 67% patients had undergone surgery (debridement, 61%; removal of foreign device, 39%; incision and drainage, 9%). Over half of the inpatients (54%) received concomitant antibiotics. Daptomycin was most frequently prescribed at a dose of 6 mg/kg/day (48%), with a median duration of therapy of 16 (range, 1–176) days. The overall clinical success rate was 85%, and was similar whether daptomycin was administered as first- or second-line therapy. The success rates achieved for infections caused by S. aureus and CoNS were 86% and 83%, respectively. Among the 79 patients who entered the long-term follow-up, 85% had a sustained response. Adverse events (AEs) and serious AEs possibly related to daptomycin were reported in 4.4% and 1.9% patients, respectively.

Results from this real-world clinical experience showed that daptomycin is an effective and well-tolerated treatment option for orthopaedic device-related infections with a high success rate up to 2 years of follow-up.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 16 - 16
1 Jan 2003
Rana B Murnaghan C Butcher I Seaton R Grigoris P
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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.