Is There a Better Way to Give Vancomycin before TKA?

    In response to increasing antibiotic resistance, vancomycin has been proposed as an alternative prophylactic agent in total knee arthroplasty (TKA).

    According to Dr. Simon Young of Mayo Clinic in Phoenix, Arizona, “Although the problem of methicillin-resistant Staphylococcus aureus, or MRSA, is well known, the most common organism in early TKA infections is coagulase-negative Staphlococci.”

    “Presently, 70-90% of these strains are resistant to cefazolin compared to less than 2% of strains when prophylactic antibiotics were first introduced in the 1960s,” he said. “We already face the reality that prophylaxis with cefalosporins does not cover the bacteria most likely to cause contamination during surgery.”

    Vancomycin can potentially cover those organisms, but it has its drawbacks as well:

    • A vancomycin infusion requires a prolonged administration time
    • Use of vancomycin risks promoting further antibiotic resistance
    • A vancomycin infusion 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.

    Dr. Young and colleagues conducted a study in 30 patients undergoing primary TKA to assess whether low-dose IORA vancomycin could achieve equal or superior tissue concentrations to systemic administration in TKA.

    Patients were randomized to 3 groups:

    • Group 1, 250 mg vancomycin
    • Group 2, 500 mg vancomycin via IORA
    • Group 3, 1 g of systemic vancomycin over 1 hour before tourniquet inflation

    In the IORA group, vancomycin was given as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet before preparation and draping and immediately before skin incision.

    Subcutaneous fat and bone samples were taken at 15-minute intervals, and antibiotic concentrations were measured using a validated technique involving liquid chromatography coupled with tandem mass spectrometry.

    The overall mean tissue concentration of vancomycin in subcutaneous fat was 14 µg/g in Group1, 44 µg/g Group 2, and 3.2 µg/g in Group 3. The mean concentration in bone was 16 µg/g in Group 1, 38 µg/g in Group 2, and 4.0 µg/g in Group 3.

    Although not a primary outcome of the study, “We saw no infections in any of the patients,” Dr. Young said. “There was no difference in clinical outcome between the groups. One patient in the systemic group developed ‘red man’ syndrome during vancomycin infusion.”

    When asked about possible drawbacks to IORA versus systemic administration, Dr. Young replied, “The main drawbacks (of IORA) are the additional 1-2 minute tourniquet time and the cost of the intraosseous needle. Complications from intraosseous infusion are rare,” he said, “and typically result from incorrect needle placement in emergency situations.”

    Dr. Young’s study demonstrated that tissue concentrations in patients receiving low-dose IORA vancomycin were equal to or higher than tissue concentrations in patients receiving systemic vancomycin. Importantly, 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.

    Dr. Young’s study may have important implications for surgeons and their practices. “One of the issues with systemic vancomycin is the prolonged infusion time, so that it is rarely given with optimum timing in a busy operating room environment and only 22% of the time in one large study,” Dr. Young said.

    “This, plus a tendency to underdose because of toxicity concerns, may account for suboptimal tissue concentrations of vancomycin at the time of surgery, possibly explaining why vancomycin appears less effective than cephalosporins against non-resistant staphylococcal species,” he said. “Low-dose IORA ensures vancomycin is given optimally, and the 4-5 times higher tissue concentrations may lead to greater efficacy.”

    As for making changes to his practice as a result of this study, Dr. Young said, “There is still controversy regarding whether routine use of vancomycin is justified in primary TKA because of the risk of promoting further resistance. In my practice, we are currently evaluating low-dose IORA vancomycin in revision TKA where the overall infection rate is higher, therefore, potentially providing greater benefit.”