Twelve patients undergoing total hip replacements were given 600mg linezolid as a 20min intravenous infusion along with conventional prophylaxis of 1gm cefamandole immediately before surgery. Routine total hip arthroplasty was performed and at timed intervals during surgery, samples of bone, fat, muscle and blood were collected for assay by HPLC analysis. Samples of haematoma fluid that formed around the operation site and further blood samples were also collected at timed intervals following the operation for assay. The penetration of linezolid into bone was rapid with mean levels of 9.1mg/L (95% CI: 7.7–10.6mg/L) achieved at 10min after the infusion, decreasing to 6.3mg/L (95% CI: 3.9–8.6mg/L) at 30min. Correcting for the simultaneous blood concentrations gave values for bone penetration of 51% at 10min, 60% at 20min and 47% at 30min. although the penetration of linezolid into fat was also rapid, mean levels and degree of penetration were approximately 60% of those seen in bone at 10min: 4.5mg/L (95%CI:3–6.1mg/L; penetration 27%) 20min: 5.2mg/L (95% CI:4–6.4mg/L; penetration 37%) and 30min:4.1mg/L (95% CI:3.3–4.8mg/L; penetration 31%). For muscle, the corresponding values were 10min: 10.4mg/L (95%CI:8.1–12.7mg/L; penetration 58%), 20min 13.4mg/L (95%:10.2–16.5mg/L; penetration 94%) and 30min 12mg/L (95% CI:9.2–14.8mg/L; penetration 93%). Mean concentration of linezolid in the haematoma around the operation site were 8.2mg/L at 6–8h and 5.6mg/L at 8–10h after the infusion and 7mg/L at 2–4h following a second 600mg infusion given 12h postoperatively. We conclude that linezolid exhibits rapid penetration in bone, fat and muscle of patients undergoing hip arthroplasty to achieve levels in excess of the MIC for sensitive organisms (MIC of <
_ 4mg/L); with therapeutic levels maintained in the drainage which surrounds the operation site for more than 16h. This pharmaco-kinetic profile is similar to those of agents currently used for the treatment of bone and associated soft tissue infections and suggests a role for linezolid in the management of such patients
