title: Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.
abstract: Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation. The penetration of linezolid into bone was rapid, with mean concentrations of 9.1 mg/L (95% CI 7.7-10.6 mg/L) achieved at 10 min after the infusion, decreasing to 6.3 mg/L (95% CI 3.9-8.6 mg/L) at 30 min. Correction for the simultaneous blood concentrations gave mean values for bone penetration of 51% at 10 min, 60% at 20 min and 47% at 30 min. Although the penetration of linezolid into fat was also rapid, mean concentrations and degree of penetration were c. 60% of those in bone; at 10 min they were 4.5 mg/L (95% CI 3.0-6.1 mg/L; penetration 27%); at 20 min they were 5.2 mg/L (95% CI 4.0-6.4 mg/L; penetration 37%); and at 30 min, 4.1 mg/L (95% CI 3.3-4.8 mg/L; penetration 31%). For muscle the corresponding values were 10.4 mg/L (95% CI 8.1-12.7 mg/L; penetration 58%) at 10 min, 13.4 mg/L (95% CI 10.2-16.5 mg/L; penetration 94%) at 20 min and 12.0 mg/L (95% CI 9.2-14.8 mg/L; penetration 93%) at 30 min. Mean concentrations of linezolid in the haematoma fluid drained from around the operation site were 8.2 mg/L at 6-8 h and 5.6 mg/L at 10-12 h after the infusion, and 7.0 mg/L at 2-4 h following a second 600 mg infusion given 12 h post-operatively. We conclude that linezolid exhibits rapid penetration into bone, fat and muscle of patients undergoing hip arthroplasty, to achieve levels in excess of its MIC for susceptible organisms (< or=4 mg/L); therapeutic concentrations were maintained in the haematoma fluid that surrounds the operation site for >16 h.
authors.affiliation: Bristol Centre for Antimicrobial Research & Evaluation and Department of Orthopaedics, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Lovering
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: G C
authors.initials: GC
authors.lastname: Bannister
authors.forename: B J A
authors.initials: BJ
authors.lastname: Lankester
authors.forename: J H M
authors.initials: JH
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: Narendra
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
mesh_terms: D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000273:Adipose Tissue / Q000378:metabolism; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D019644:Arthroplasty, Replacement, Hip; D001842:Bone and Bones / Q000378:metabolism; D002435:Cefamandole / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006406:Hematoma / Q000378:metabolism; D006621:Hip Joint / Q000601:surgery; D006801:Humans; D000069349:Linezolid; D009132:Muscles / Q000378:metabolism; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D002435:Cefamandole; D000069349:Linezolid