RESUMEN
AIM: To test antibiotic-loaded coating for efficacy in reducing bacterial biofilm and development of osteomyelitis in an orthopaedic model of implant infection. METHODS: Phosphatidylcholine coatings loaded with 25% vancomycin were applied to washed and sterilized titanium wires 20 mm in length. A 10 mm segment was removed from rabbit radius (total = 9; 5 coated, 4 uncoated), and the segment was injected with 1 × 10(6) colony forming units (CFUs) of Staphylococcus aureus (UAMS-1 strain). Titanium wires were inserted through the intramedullary canal of the removed segment and into the proximal radial segment and the segment was placed back into the defect. After 7 d, limbs were removed, X-rayed, swabbed for tissue contamination. Wires were removed and processed to determine attached CFUs. Tissue was swabbed and streaked on agar plates to determine bacteriological score. RESULTS: Antibiotic-loaded coatings resulted in significantly reduced biofilm formation (4.7 fold reduction in CFUs; P < 0.001) on titanium wires and reduced bacteriological score in surrounding tissue (4.0 ± 0 for uncoated, 1.25 ± 0.5 for coated; P = 0.01). Swelling and pus formation was evident in uncoated controls at the 7 d time point both visually and radiographically, but not in antibiotic-loaded coatings. CONCLUSION: Active antibiotic was released from coated implants and significantly reduced signs of osteomyelitic symptoms. Implant coatings were well tolerated in bone. Further studies with additional control groups and longer time periods are warranted. Antibiotic-loaded phosphatidylcholine coatings applied at the point of care could prevent implant-associated infection in orthopaedic defects.
RESUMEN
BACKGROUND: Orthopaedic biomaterials are susceptible to biofilm formation. A novel lipid-based material has been developed that may be loaded with antibiotics and applied as an implant coating at point of care. However, this material has not been evaluated for antibiotic elution, biofilm inhibition, or in vivo efficacy. QUESTIONS/PURPOSES: (1) Do antibiotic-loaded coatings inhibit biofilm formation? (2) Is the coating effective in preventing biofilm in vivo? METHODS: Purified phosphatidylcholine was mixed with 25% amikacin or vancomycin or a combination of 12.5% of both. A 7-day elution study for coated titanium and stainless steel coupons was followed by turbidity and zone of inhibition assays against Staphylococcus aureus and Pseudomonas aeruginosa. Coupons were inoculated with bacteria and incubated 24 hours (N = 4 for each test group). Microscopic images of biofilm were obtained. After washing and vortexing, attached bacteria were counted. A mouse biofilm model was modified to include coated and uncoated stainless steel wires inserted into the lumens of catheters inoculated with a mixture of S aureus or P aeruginosa. Colony-forming unit counts (N = 10) and scanning electron microscopy imaging of implants were used to determine antimicrobial activity. RESULTS: Active antibiotics with colony inhibition effects were eluted for up to 6 days. Antibiotic-loaded coatings inhibited biofilm formation on in vitro coupons (log-fold reductions of 4.3 ± 0.4 in S aureus and 3.1 ± 0 for P aeruginosa in phosphatidylcholine-only coatings, 5.6 ± 0 for S aureus and 3.1 ± 0 for P aeruginosa for combination-loaded coatings, 5.5 ± 0.3 for S aureus in vancomycin-loaded coatings, and 3.1 ± 0 for P aeruginosa for amikacin-loaded coatings (p < 0.001 for all comparisons of antibiotic-loaded coatings against uncoated controls for both bacterial strains, p < 0.001 for comparison of antibiotic-loaded coatings against phosphatidylcholine only for S aureus, p = 0.54 for comparison of vancomycin versus combination coating in S aureus, P = 0.99 for comparison of antibiotic- and unloaded phosphatidylcholine coatings in P aeruginosa). Similarly, antibiotic-loaded coatings reduced attachment of bacteria to wires in vivo (log-fold reduction of 2.54 ± 0; p < 0.001 for S aureus and 0.83 ± 0.3; p = 0.112 for P aeruginosa). CONCLUSIONS: Coatings deliver active antibiotics locally to inhibit biofilm formation and bacterial growth in vivo. Future evaluations will include orthopaedic preclinical models to confirm therapeutic efficacy. CLINICAL RELEVANCE: Clinical applications of local drug delivery coating could reduce the rate of implant-associated infections.