The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional versus systemic prophylaxis in TKA: a randomized trial

Abstract

Background: 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.

Questions/purposes: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figures

Fig. 1A–B

Images show (A) insertion of the intraosseous needle using a sterilized driver and (B) the needle in situ allowing injection of the antibiotic, occurring after tourniquet inflation and before skin incision. Reprinted with permission of Vidacare Corp (www.vidacare.com).

Fig. 2

A graph show the tissue concentrations of vancomycin in subcutaneous fat at each sample point. The 250-mg IORA group is in blue, 500-mg IORA group in orange, and 1-g systemic group in green. Concentrations on log scale: 2 = 7 μg/g, 4 = 55 μg/g, and 6 = 403 μg/g. Box represents the median; horizontal line in box represents the 25% and 75% quartiles; whiskers represent 1.5 times the interquartile range from the box.

Fig. 3

A graph shows the tissue concentrations of vancomycin in bone at each sample point. The 250-mg IORA group is in blue, 500-mg IORA group in orange, and 1-g systemic group in green. Concentrations on log scale: 1 = 3 μg/g, 2 = 7 μg/g, 3 = 20 μg/g, 4 = 55 μg/g, and 5 = 148 μg/g. Box represents the median; horizontal line in box represents the 25% and 75% quartiles; whiskers represent 1.5 times the interquartile range from the box.

Fig. 4

A Loess graph shows the systemic blood concentrations of vancomycin with predicted CIs in the three intervention groups.