Vancomycin bone and tissue concentrations following tibial intraosseous administration – evaluated in a porcine model

Abstract

Abstract. Introduction. Systemic perioperative vancomycin may not provide sufficient prophylactic target-site concentrations in the prevention of prosthetic joint infections. Intraosseous vancomycin potentially provides high target-site concentrations. The objective of the present study was to evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model. Methods. Eight pigs received 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. No tourniquet was applied. Microdialysis was applied for sampling of vancomycin concentrations in adjacent tibial cancellous bone, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained as a systemic reference. Samples were collected for 12 h. Results. High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1236 (range 28–5295) µg/mL, which remained high throughout the sampling period. The mean (standard deviation) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. Peak drug concentration, time to peak drug concentration, and area under the concentration–time curve were within the same range in the intramedullary canal, the synovial fluid of the knee, and the subcutaneous tissue. Conclusion. Tibial intraosseous administration of vancomycin provided high concentrations in tibial cancellous bone throughout a 12 h period but with an unpredictable and wide range of peak concentration. The systemic absorption was high and immediate, thus mirroring an intravenous administration. Low mean concentrations were found in all the remaining compartments.

Concentrations of co-administered vancomycin and meropenem in the internal dead space of a cannulated screw and in cancellous bone adjacent to the screw – Evaluated by microdialysis in a porcine model

“…To extend the T > MIC for both drugs, and hereby ensure a more theoretically adequate antibiotic prophylaxis, alternative or more aggressive dosing regimens may be considered. Vancomycin has shown high and long-lasting target tissue concentrations when applied locally [25] , while meropenem has shown longer T > MIC, a need for lower daily dosages, and significantly higher cure rates when administered continuously rather than intermittent [26][27][28] . Continuous infusion has also been associated with a lower risk of resistance development [29] .…”

High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace—A Microdialysis Porcine Study

“…Microdialysis is a catheter-based method for continuous sampling of the free unbound and active fraction of antibiotics in the interstitial space of the tissue of interest [ 43 , 44 , 45 ]. A semipermeable membrane at the tip of the catheter allows solutes to diffuse along the concentration gradient, but without achieving equilibrium, as the microdialysis catheter is constantly perfused.…”

“…Microdialysis is a catheter-based method for continuous sampling of the free unbound and active fraction of antibiotics in the interstitial space of the tissue of interest [43][44][45].…”