Summary
Systemic and intra-articular vancomycin concentrations following ACL reconstruction with vancomycin-soaked autografts peak after its half-live and remain well below toxic thresholds, confirming a prolonged sponge effect and a favorable safety profile.
Abstract
Background
Vancomycin soaking of anterior cruciate ligament (ACL) grafts has been shown to significantly reduce the incidence of postoperative infections and is emerging as a gold standard in ACL reconstruction. However, systemic vancomycin exposure and intra-articular concentrations remain poorly understood. This study aims to assess serum vancomycin levels over 48 hours following ACL reconstruction and determine whether intra-articular concentrations exceed the known chondrotoxic threshold of 1000 µg/ml. We hypothesized that vancomycin would be systemically detectable at low levels, peaking shortly after tourniquet release, and that intra-articular concentrations would remain well below chondrotoxic thresholds.
Methods
A prospective observational study was conducted including 22 patients undergoing ACL reconstruction with hamstring or quadriceps tendon autografts soaked in 5 mg/ml vancomycin. Systemic vancomycin levels were measured via blood samples taken at seven time points: preoperatively, after cefazolin administration, 10 minutes post-tourniquet release, and at 1h, 6-8h, 24h, and 48h postoperatively. In a separate cohort of 20 patients, intra-articular vancomycin levels were measured in synovial fluid aspirated immediately after wound closure. Vancomycin concentrations were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman rho correlation coefficients and t-tests were applied to identify relationships between variables, with significance set at p<0.05.
Results
In the systemic analysis, 21 patients (17 men, 4 women; mean age 36.2 ± 9.6 years) were included. Vancomycin was detectable in serum at low concentrations, with an initial mean of 0.0031 ± 0.0085 µg/ml immediately after tourniquet release. The highest mean concentration of 0.0120 ± 0.0173 µg/ml was observed at 24h, indicating a sustained release from the graft. The maximum single measurement was 0.704 µg/ml at 6-8h postoperatively. No significant correlation was found between systemic vancomycin levels and patient-specific factors (BMI, age, graft diameter, or soaking duration).
In the synovial fluid analysis, 20 patients (15 women, 5 men; mean age 29.35 ± 11.3 years) were included. The mean intra-articular vancomycin concentration was 23.23 ± 21.68 µg/ml, with a range of 2.32 to 71.56 µg/ml. No sample approached the chondrotoxic threshold of 1000 µg/ml. There was no significant difference in vancomycin concentrations between semitendinosus and quadriceps tendon grafts (p=0.911), and no correlation was observed between vancomycin concentration and graft diameter or duration from implantation to aspiration.
Conclusion
Vancomycin-soaked ACL grafts release low but detectable levels of vancomycin systemically, peaking at 24h postoperatively. In contrast to the hypothesis, the peak concentration after its half-live supports a constant release of antibiotics from the soaked graft. Intra-articular vancomycin concentrations remain well below chondrotoxic levels, reinforcing the safety of this prophylactic technique. Given the strong evidence for infection prevention and the absence of systemic toxicity or chondrotoxicity, vancomycin-soaking of ACL grafts is a viable and safe adjunct in ACL reconstruction.