Abstract
Aim
The incidence of orthopaedic methicillin-resistant staphylococcus aureus infections is increasing. Vancomycin may therefore play an increasingly important role in orthopaedic perioperative antimicrobial prophylaxis. Adequate antimicrobial concentrations at target site is essential for prevention of orthopaedic infections. Current studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. The aim of this study was therefore to assess the concentration of vancomycin in plasma, subcutaneous tissue and bone after single dose administration using microdialysis (MD) in patients undergoing total knee replacement.
Method
1,000 mg of vancomycin was postoperatively administered intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, subcutaneous tissue (SCT), cancellous and cortical bone were measured the following 8 hours. MD was applied for sampling in solid tissues. The vancomycin concentration in MD-samples was determined using ultra-high performance liquid chromatography, whilst the free plasma concentration was determined using a chemistry analyzer*.
Results
For all extravascular tissue, an impaired penetration was demonstrated, with lower area under the concentration-time curve (AUC) compared to free plasma. The lowest AUC was found in cortical bone. For all tissues, tissue penetration expressed as the ratio of the area under the concentration–time curve from 0 to the last measured value (AUC0-last tissue/AUC0-last plasma) were below 0.5. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2 mg/L were 3, 36, 27 and 110 min for plasma, SCT, cancellous and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4 mg/L was not reached in cortical bone. The AUC0-last and peak drug concentrations (Cmax) for SCT, cancellous and cortical bone were lower than those of free plasma. The time to Cmax was higher for all tissues compared with free plasma.
Conclusions
Penetration of vancomycin to bone and SCT was found to be impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached at target site using standard prophylactic dosage.
*Cobas c501
