Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement.

ABSTRACT

We have studied the mechanical and pharmacokinetic characteristics of an industrially-prepared bone cement containing 3 g of vancomycin per 60 g cement. A low viscosity cement was selected, to increase contact between the antibiotic and the infected surfaces. Resistance of compression (95 mPa) was well above the required standard (70 mPa) and similar to that of other cements with or without gentamicin. The concentrations in blood, urine and bone were measured in mg/l and mg/kg, and compared to the break point (BP) of susceptibility tests, which must be obtained to achieve control of infection. Diffusion tests were conducted in vitro (elution in saline from rods), and in 30 sheep femora implanted with the cement in vivo. In the animal study, bone levels during the first three months were three-fold higher than the BP (i.e., were > or = 12 mg/l) in 92% of specimens from all areas of bone studied and at all times since implantation; they exceeded five times the BP in 56% of specimens and were never lower than twice the BP. The mean level was four times the BP after six months and fell sharply during the next six months. A pharmacokinetic study in ten patients who had a primary total hip arthroplasty with vancomycin-loaded cement as prophylactic antibiotic therapy showed that blood levels were lower than 3 micrograms/ml, i.e., 30 times lower than the toxic threshold (90 micrograms/ml). Vancomycin was undetectable in urine after the tenth day. The levels in drainage fluids were five times the BP after 24 h and equal to it after four days. None of the ten patients treated prophylactically with vancomycin-loaded cement developed evidence of allergy, toxicity, intolerance or loosening during a two year period. No adverse events were recorded in 17 other patients treated with a vancomycin (2 g) plus gentamicin (0.8 g) loaded cement as adjuvant therapy for severe prosthetic infection.