Therapeutic Efficacy of an Erythromycin-Loaded Coaxial Nanofiber Coating in a Rat Model of S. aureus-Induced Periprosthetic Joint Infection.

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm2) was greater than controls and EM0 (0.390 mm2 and 0.0 mm2, respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm2). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.

Efficacy of Commercially Available Irrigation Solutions on Removal of Staphylococcus Aureus and Biofilm From Porous Titanium Implants: An In Vitro Study.

BACKGROUND: Periprosthetic joint infection remains a major problem. The bactericidal efficacy of commercial irrigation solutions for the treatment of infection is not well established in the presence of porous titanium (Ti) implants. This study compared the in vitro efficacy of five irrigation solutions on infected three-dimensional-printed porous Ti discs. METHODS: Titanium discs (2 × 4 mm, 400, 700, and 1,000 µm) were infected with S. aureus (1 × 106 colony-forming unit/mL) and incubated for 3 hours or 3 days to create acute or chronic infection with biofilm. Discs were irrigated with saline, antibiotic, or antiseptic solutions, then repeatedly sonicated. Sonicates were cultured for bacterial quantification. Statistical analyses were performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc testing (P < .05 significance). Biofilms were visualized by scanning electron microscopy. RESULTS: Saline irrigation was ineffective in both groups. In acute infections with 400 µm pores, differences were found with saline versus solution #3 (P = .015) and #4 (P = .015). Solution #4 had the lowest bacterial counts for all pore sizes. For biofilm, irrigation with saline, solutions #1, #2, and #3 inadequately cleared bacteria in all pore sizes. Lower remaining concentrations were observed in #4 with 400µm pores compared to saline (P = .06) and #2 (P = .039). The scanning electron microscopy showed a reduction of biofilm in samples washed with #4. CONCLUSIONS: Irrigation of infected porous Ti discs with saline, solutions #1 and #2 failed to reduce the bacterial load. The 400 µm discs consistently had more bacteria despite irrigation, highlighting the difficulty of removing bacteria from small pores. Solutions #3 and #4 reduced bacteria acutely, but only #4 demonstrated efficacy in clearing biofilm compared to saline. These results should be considered when treating periprosthetic joint infection in the presence of porous components and the potential presence of biofilm.

Effects of Vancomycin/Tobramycin-Doped Ceramic Composite (Polyvinyl Alcohol Composite-Vancomycin/Tobramycin-Polymeric Dicalcium Phosphate Dihydrate) in a Rat Femur Model Implanted With Contaminated Porous Titanium Cylinders.

BACKGROUND: Periprosthetic joint infection (PJI) remains common and problematic. We hypothesized that using a bioceramic that provided rapid release of the antibiotics (vancomycin [VAN] or VAN and tobramycin [VAN and TOB]) from a polyvinyl-alcohol-composite (PVA) combined with a delayed and sustained antibiotic release from polymeric-dicalcium-phosphate-dihydrate (PDCPD) ceramic would inhibit S. aureus-associated implant infections. METHODS: A total of 50 male Sprague Dawley rats were randomly divided into 5 groups-I: negative control; II: bacteria only; III: bacteria + saline wash; IV: bacteria + PVA-VAN-PDCPD, and V: bacteria + PVA-VAN-TOB-PDCPD. A porous titanium (Ti) implant was press-fit into the rat knee. S. aureus-containing broth was added into the joint space creating a PJI. After 1 week, the joints from groups III to V were washed with saline and the fluid collected for bacterial quantification. This was followed by saline irrigation treatment (groups III to V) and application of the antibiotic-loaded PVA-PDCPD bioceramic (groups IV and V). On day 21, joint fluid was collected, and the implants harvested for bacterial quantification. RESULTS: No bacteria were isolated from the negative control (group I). The positive control (group II) was positive on both days 7 and 21. Bacteria were still present on day 21 in the fluid and implant in group III. Groups (IV and V) showed a decrease in the bacterial burden in the fluid and implant on day 21. There were significant differences in bacteria levels in the collected wash fluid and on the implant at day 21 between the saline wash (group III) and treatment groups (IV and V). CONCLUSIONS: In this animal model of acute periprosthetic infection, treatment with PVA-VAN-PDCPD and PVA-VAN/TOB-PDCPD reduced bacterial load in the infected joint and the infected Ti implant. Application of PVA-VAN-PDCPD and/or PVA-VAN/TOB-PDCPD after saline irrigation could be used as an addition to the treatment of PJI.