Bacterial biofilms are highly antibiotic resistant microbial cell associations that lead to chronic infections. Unlike free-floating planktonic bacterial cells, the biofilms are encapsulated in a hardly penetrable extracellular polymeric matrix and, thus, demand innovative approaches for treatment. Recent advancements on the development of gel-nanocomposite systems with tailored therapeutic properties provide promising routes to develop novel antimicrobial agents that can be designed to disrupt and completely eradicate preformed biofilms. In our study, we developed a unique thermoresponsive magnetic glycol chitin-based nanocomposite containing d-amino acids and iron oxide nanoparticles, which can be delivered and undergoes transformation from a solution to a gel state at physiological temperature for sustained release of d-amino acids and magnetic field actuated thermal treatment of targeted infection sites. The d-amino acids in the hydrogel nanocomposite have been previously reported to inhibit biofilm formation and also disrupt existing biofilms. In addition, loading the hydrogel nanocomposite with magnetic nanoparticles allows for combination thermal treatment following magnetic field (magnetic hyperthermia) stimulation. Using this novel two-step approach to utilize an externally actuated gel-nanocomposite system for thermal treatment, following initial disruption with d-amino acids, we were able to demonstrate in vitro the total eradication of Staphylococcus aureus biofilms, which were resistant to conventional antibiotics and were not completely eradicated by separate d-amino acid or magnetic hyperthermia treatments.
Background: Revision total knee arthroplasty (rTKA) is associated with significant risk of wound-related morbidity. The present study aimed to evaluate the 1) efficacy of closed-incision negative-pressure therapy (ciNPT) vs silver-impregnated antimicrobial dressing (AMD) in mitigating postoperative surgical site complications (SSCs), 2) the effect of ciNPT vs AMD on certain postoperative health utilization parameters, and on 3) patient-reported outcomes (PROs) improvement at 90-day postoperative follow-up. Methods: This multicenter randomized controlled trial was conducted between December 2017 and August 2019. Patients !22 years, at high risk for SSC, and receiving rTKA with full exchange and reimplantation of new prosthetic components or open reduction and internal fixation of periprosthetic fractures were screened for inclusion. Eligible patients were randomized to receive a commercially available ciNPT system or a silver-impregnated AMD (n ¼ 147, each) for minimum of 5-day duration. Primary outcome was the 90-day incidence of SSCs with stratification in accordance with revision type (aseptic/septic). Secondary outcomes were the 90-day health care utilization parameters (readmission, reoperation, dressing changes, and visits) and PROs. Results: Of 294 patients randomized (age: 64.9 ± 9.0 years, female: 59.6%), 242 (82.0%) patients completed the study (ciNPT: n ¼ 124; AMD: n ¼ 118). The incidence of 90-day SSCs was lower for the ciNPT cohort (ciNPT: 3.4% vs AMD: 14.3%; odds ratio (OR): 0.22, 95% confidence interval (0.08, 0.59); P ¼ .0013). Readmission rates (3.4% vs 10.2%, OR: 0.30(0.11, 0.86); P ¼ .0208) and mean dressing changes (1.1 ± 0.3 vs 1.3 ± 1.0; P ¼ .0003) were lower with ciNPT. The differences in reoperation rates, number of visits, and PRO improvement between both arms were not statistically significant (P > .05). Conclusion: ciNPT is effective in reducing the 90-day postoperative SSCs, readmission, and number of dressing changes after rTKA. Recommending routine implementation would require true-cost analyses.
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