Presented by: Juan Sebastian Rodriguez-Alvarez MD
Cleveland Clinic Glickman Urological and Kidney Institute/Research Fellow

Introduction

Device-associated infections, particularly arising from urinary catheters and stents are frequent causes of healthcare related infections. These infections are often associated with biofilm formation and ultimately require device removal. Escherichia Coli is one of the most commonly isolated bacteria in such biofilms. Silver coatings have been used to minimize infections due to its intrinsic antibacterial properties, and gold-silver mixtures have superior antimicrobial activity. We designed novel antimicrobial nanoparticles (NP) composed of silver and gold with polyhydroxy-fullerenes (PHF); proposed to enhance reactive oxygen species formation. Coatings of these novel NPs were evaluated for antimicrobial and anti-biofilm formation properties against E. coli. 

Materials

PHF was used for synthesizing gold (AuNP), silver (AgNP), gold-silver bimetallic (AuAgNP) and silver-platinum bimetallic (AgPtNP) NPs. Resulting mixtures were coated on polyurethane discs. To induce biofilm formation on surfaces, coated and uncoated discs were incubated overnight in broth containing E. coli. The resulting broth was sampled and serially diluted to evaluate bactericidal properties of the NP coatings on E. coli. Biofilms were detached from the discs into phosphate-buffered saline, then serially diluted. All dilutions were incubated for quantification of colony forming units (CFU) and CFU/mL. All experiments were done in triplicate.

Results

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AuNP did not show any significant antibacterial or anti-biofilm activity whereas AgNP showed a bactericidal effect with a mean 3.2-log reduction of E. coli CFUs compared to uncoated controls (p<0.001). Antibacterial activity of AgPtNP was similar to AgNP. In contrast, a significant bactericidal effect was observed with AuAgNP with a mean 5-log reduction. This was further investigated by testing a 1:1 mixture of AuNP and AgNP, which showed a mean 8.5-log reduction, suggesting a strong synergetic effect between gold and silver NPs. Most of these reductions were also observed for anti-biofilm activity (Figure 1). 

Conclusion

A combined gold and silver nanoparticle coating with large antibacterial and antibiofilm activity could potentially reduce implant colonization and associated infections.

Funding

Cleveland Clinic Caregiver Catalyst Award, Lerner Research Institute Seed Funds

Lead Authors

Juan Sebastian Rodriguez-Alvarez, MD
Cleveland Clinic Glickman Urological and Kidney Institute

Co-Authors

Yue Xu, MSc
Cleveland Clinic Lerner Research Institute

Smita De, MD, PhD
Cleveland Clinic Glickman Urological and Kidney Institute

Jorge Gutierrez-Aceves, MD
Cleveland Clinic Glickman Urological and Kidney Institute

Vijay Krishna, PhD
Cleveland Clinic Lerner Research Institute