High active local levels of vancomycin without nephrotoxicity released from impacted bone allografts in 20 revision hip arthroplasties

Background Cancellous bone can act as a delivery vehicle for vancomycin without impairment of graft incorporation. However, local and systemic antibiotic levels, biological activity of vancomycin, interaction with antibiotic-loaded cement, and also nephrotoxicity of these composites have not yet been studied clinically.

Material and methods Blood, drainage and urine samples of 20 consecutive patients undergoing revision total hip arthroplasties with impaction grafting technique utilizing 1 g of vancomycin per femoral head were studied. Plain PMMA cement was used in 10 cases, while PMMA with gentamycin was used in 5 cases and tobramycin was used in the remaining 5 cases. Biological activity of vancomycin was studied using kinetic killing curves in three ATCC organisms (methicillin-sensitive Staphylococcus aureus,methicillin-resistant Staphylo-coccus aureusand Pseudomonas aeruginosas).Quantification was done with fluorescent polarized immunoassay. Renal function was evaluated with preoperative and postoperative urea and creatinine.

Results Local active bactericidal levels of vancomycin reached 1 400 μg/mL (average 5-point level = 367 μg/mL) without nephrotoxicity. Vancomycin was present in urine until the fifteenth day. Both aminoglycosides in the cement had activity against Pseudomonas aeruginosas.

Interpretation Local levels of vancomycin were 35 times greater than the highest levels reported with vancomycin-loaded PMMA. A synergistic effect was observed between vancomycin released from impacted allografts and aminoglycoside-loaded PMMA.