Abstract
Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalisation, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intra-articular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks.
The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration. Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (trough levels of 8.4 and 4.2 μg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was determined to be 3.06 hours.
This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included debridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 μg/mL. Mean serum vancomycin peak concentration was 6±2 μg/mL and the mean serum vancomycin trough concentration was 3±1 μg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 μg/mL and 20,167 μg/mL and trough concentrations were 724 μg/mL and 543μg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean follow-up was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83±9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively.
Directly infusing antibiotics into the infected area maintains a high local concentration level while minimising systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics.
