The Mark Coventry Award: Higher Tissue Concentrations of Vancomycin With Low-dose Intraosseous Regional Versus Systemic Prophylaxis in TKA

A Randomized Trial



In response to increasing antibiotic resistance, vancomycin has been proposed as an alternative prophylactic agent in TKA. However, vancomycin requires a prolonged administration time, risks promoting further antibiotic resistance, and can cause systemic toxicity. Intraosseous regional administration (IORA) is known to achieve markedly higher antibiotic concentrations than systemic administration and may allow the use of a lower vancomycin dose.


We assessed whether low-dose IORA vancomycin can achieve tissue concentrations equal or superior to those of systemic administration in TKA and compared complications between patients treated with IORA and intravenous vancomycin.


We randomized 30 patients undergoing primary TKA to receive 250 or 500 mg vancomycin via IORA or 1 g via systemic administration. IORA was performed as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet immediately before skin incision. Subcutaneous fat and bone samples were taken during the procedure and antibiotic concentrations measured.


The overall mean tissue concentration of vancomycin in subcutaneous fat was 14 μg/g in the 250-mg IORA group, 44 μg/g in the 500-mg IORA group, and 3.2 μg/g in the systemic group. Mean concentrations in bone were 16 μg/g in the 250-mg IORA group, 38 μg/g in the 500-mg IORA group, and 4.0 μg/g in the systemic group. One patient in the systemic group developed red man syndrome during infusion.


Low-dose IORA vancomycin results in tissue concentrations equal or superior to those of systemic administration. IORA optimizes timing of vancomycin administration, and the lower dose may reduce the risk of systemic side effects while providing equal or enhanced prophylaxis in TKA.

Level of Evidence

Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

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We thank Irene Zeng MSc (Hons) for her assistance with statistical analysis and the Awhina Trust for their funding support, and we thank Dr Kelly Vince for his advice and guidance on the project. We also thank Vidacare Corp for supplying the intraosseous needles without charge.

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Corresponding author

Correspondence to Simon W. Young FRACS.

Additional information

The institution of one or more of the authors (MZ, GAM) received funding from the Awhina Trust (Auckland, New Zealand), a charitable trust with no relationship to the subject of this article.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.

Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

Procedures and sample collection were performed at North Shore Hospital, Auckland, New Zealand. Sample analysis was performed at Canterbury Health Laboratories, Christchurch, New Zealand.

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Young, S.W., Zhang, M., Freeman, J.T. et al. The Mark Coventry Award: Higher Tissue Concentrations of Vancomycin With Low-dose Intraosseous Regional Versus Systemic Prophylaxis in TKA. Clin Orthop Relat Res 472, 57–65 (2014).

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  • Vancomycin
  • Teicoplanin
  • Femoral Nerve Block
  • Vancomycin Concentration
  • High Tissue Concentration