PHARMACOKINETICS, USES, AND LIMITATIONS OF VANCOMYCIN-LOADED BONE-CEMENT

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 compre ssion (95 mPa) was well above the required standard (70 mPa) and simil ar to that of other cements with or without gentamicin. The concentrat ions in blood, urine and bone were measured in mg/l and mg/kg, and com pared to the break point (BP) of susceptibility tests, which must be o btained to achieve control of infection. Diffusion tests were conducte d in vitro (elution in saline from rods), and in 30 sheep femora impla nted with the cement in vivo. In the animal study, bone bevels during the first three months were three-fold higher than the BP (i.e., were 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 s pecimens and were never lower than twice the BP. The mean level was fo ur times the BP after six months and fell sharply during the next six months. A pharmacokinetic study in ten patients who had a primary tota l hip arthroplasty with vancomycin-loaded cement as prophylactic antib iotic therapy showed that blood levels were bower than 3 mu g/ml, i.e. , 30 times lower than the toxic threshold (90 mu g/ml). Vancomycin was undetectable in urine after the tenth day. The levels in drainage flu ids were five times the BP after 24 h and equal to it after four days. None of the ten patients treated prophylactically with vancomycin-loa ded cement developed evidence of allergy toxicity, intolerance or loos ening 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.