Silver Carboxylate-Eluting Titanium-Dioxide Polydimethylsiloxane Coating Inhibits Multi-Drug-Resistant Acinetobacterium baumannii and Vancomycin-Resistant Enterococcus faecalis Adherence and Proliferation on Orthopedic Trauma Fixation and Spinal Fusion Materials.

Background: Vancomycin-resistant Enterococcus faecalis and multi-drug-resistant (MDR) Acinetobacter baumannii are rising contributors to spinal fusion and fracture-associated infections (FAI), respectively. These MDR bacteria can form protective biofilms, complicating traditional antibiotic treatment. This study explores the effects of the antibiotic-independent antimicrobial silver carboxylate (AgCar)-doped coating on the adherence sand proliferation of these pathogens on orthopedic implant materials utilized in spinal fusion and orthopedic trauma fixation. Methods: Multi-drug-resistant Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis were inoculated on five common implant materials: cobalt chromium, titanium, titanium alloy, polyether ether ketone, and stainless steel. Dose response curves were generated to assess antimicrobial potency. Scanning electron microscopy and confocal laser scanning microscopy were utilized to characterize and quantify growth and adherence on each material. Results: The optimal AgCar concentration was a 95% titanium dioxide (TiO2)-5% polydimethylsiloxane (PDMS) matrix combined with 10 × silver carboxylate, which inhibited bacterial proliferation by 89.40% (p = 0.001) for MDR Acinetobacter baumannii and 84.02% (p = 0.001) for vancomycin-resistant Enterococcus faecalis compared with uncoated implants. A 95% TiO2-5% PDMS matrix combined with 10 × AgCar was equally effective at inhibiting bacterial proliferation across all implant materials for MDR Acinetobacter baumannii (p = 0.19) and vancomycin-resistant Enterococcus faecalis (p = 0.07). A 95% TiO2-5% PDMS matrix with 10 × AgCar is effective at decreasing bacterial adherence of both MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis on implant materials. Conclusions: Application of this antibiotic-independent coating for surgery in which these implant materials might be used may prevent adherence, biofilm formation, spinal infections, and FAI by MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis.

Silver as an Antibiotic-Independent Antimicrobial: Review of Current Formulations and Clinical Relevance.

Background: The increase of multi-drug-resistant organisms has revived the use of silver as an alternative antibiotic-independent antimicrobial. Although silver's multimodal mechanism of action provides low risk for bacterial resistance, high local and uncontrolled concentrations have shown toxicity. This has resulted in efforts to develop novel silver formulations that are safer and more predictable in their application. Optimization of silver as an antimicrobial is crucial given the growing resistance profile against antibiotics. This article reviews formulations of silver used as antimicrobials, focusing on the mechanisms of action, potential for toxicity, and clinical applications. Methods: A search of four electronic databases (PubMed, Embase, MEDLINE, and Cochrane Library) was conducted for relevant studies up to January 2022. Searches were conducted for the following types of silver: ionic, nanoparticles, colloidal, silver nitrate, silver sulfadiazine, silver oxide, silver carboxylate, and AQUACEL® (ConvaTec, Berkshire, UK). Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. Results: A review of the antimicrobial activity and uses of ionic silver, silver nanoparticles, colloidal silver, silver nitrate, silver sulfadiazine, silver oxide, Aquacel, and silver carboxylate was conducted. The mechanisms of action, clinical uses, and potential for toxicity were studied, and general trends between earlier and more advanced formulations noted. Conclusions: Early forms of silver have more limited utility because of their uncontrolled release of silver ions and potential for systemic toxicity. Multiple new formulations show promise; however, there is a need for more prospective in vivo studies to validate the clinical potential of these formulations.

Silver Carboxylate as an Antibiotic-Independent Antimicrobial: A Review of Current Formulations, in vitro Efficacy, and Clinical Relevance.

The increasing prevalence of multi-drug resistant pathogens has led to a renewed focus on the use of silver as an antibiotic-independent antimicrobial. Unfortunately, the use of many silver formulations may be limited by an uncontrolled release of silver with the potential for significant cytotoxic effects. Silver carboxylate (AgCar) has emerged as an alternative formulation of silver with the potential to mitigate these concerns while still displaying significant bactericidal activity. This article reviews the efficacy of silver carboxylate formulations as a promising novel antibiotic-independent antimicrobial. This study was conducted through a search of five electronic databases (PubMed, Embase, MEDLINE, Cochrane Library, and Web of Science) for relevant studies up to September 2022. Searches were conducted for types of "silver carboxylate" formulations. Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. A review of the antimicrobial activity and cytotoxicity of silver carboxylate was compiled based on this search. Current body of data suggests that silver carboxylate shows promise as an emerging antibiotic-independent antimicrobial, with significant bactericidal effects while minimizing cytotoxicity. Silver carboxylate addresses several of the limitations of more primitive formulations, including controlled dosing and fewer negative effects on eukaryotic cell lines. These factors are concentration-dependent and largely rely on the vehicle system used to deliver it. Although several silver carboxylate-based formulations like titanium dioxide/polydimethylsiloxane (TiO2/PDMS) matrix-eluting AgCar have shown promising results in vitro, and could potentially be utilized independently or in conjunction with current and future antimicrobial therapies, there is a need for further in vivo studies to validate their overall safety and efficacy profile.