Abstract
Aim
In vivo studies have shown a preventive and curative effect of using an injectable vancomycin containing biphasic ceramic in an osteomyelitis model. No clinical long term pharmacokinetic release study has been reported. Inadequate concentration in target tissues results in treatment failure and selection pressure for antibiotic-resistant organisms.
Our hypothesis was that vancomycin in the first week would reach high local concentrations but with low systemic levels.
Method
9 patients (6 women, 3 men) with trochanteric hip fractures classified as A1 and A2 according to the AO-classification all had internal fixations. The mean age was 75.3 years (± S.D. 12.3 years, range 44–84y). An injectable ceramic with hydroxyapatite embedded in a calcium sulphate matrix containing 66mg vancomycin per mL augmented the fixation. A mean of 9.7 mL (± S.D. 0.7 mL, range 8–10mL) was used. The elution of vancomycin was followed by collecting drain fluid, blood (4 days) and urine (4 weeks)
Results
The concentration of antibiotics in the drain showed an important burst during the first 12h after surgery, with a mean value of 709.9 µmol/L (± S.D. 383.9), which decreased linearly to a mean value of 60.9 µmol/L at 2.5 days. In the urine, the vancomycin concentration reached 68.9 µmol/L (± S.D. 34.4) during the first day, which was decreased logarithmic over the first two weeks to reach zero at 20 days (see Figure). The systemic concentration of vancomycin was constantly low, not exceeding 2.6 µmol/L.
Conclusions
This is the first long term pharmacokinetic study reporting vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels (wound drainage), sustained and complete release at three weeks (verified by the urine concentrations), and systemic concentrations well below toxic levels. This system should be useful in preventing and treating bone infection.
