The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection

Abstract

Peri-prosthetic infections are notoriously difficult to treat as the biomaterial implant is ideal for bacterial adhesion and biofilm formation, resulting in decreased antibiotic sensitivity. Previously, we reported that vancomycin covalently attached to a Ti alloy surface (Vanc-Ti) could prevent bacterial colonization. Herein we examine the effect of this Vanc-Ti surface on Staphylococci epidermidis, a Gram-positive organism prevalent in orthopaedic infections. By direct colony counting and fluorescent visualization of live bacteria, S. epidermidis colonization was significantly inhibited on Vanc-Ti implants. In contrast, the gram-negative organism Escherichia coli readily colonized the Vanc-Ti rod, suggesting retention of antibiotic specificity. By histochemical and SEM analysis, Vanc-Ti prevented S. epidermidis biofilm formation, even in the presence of serum. Furthermore, when challenged multiple times with S. epidermidis, Vanc-Ti rods resisted bacterial colonization. Finally, when S. epidermidis was continuously cultured in the presence of Vanc-Ti, the bacteria maintained a Vanc sensitivity equivalent to the parent strain. These findings indicate that antibiotic derivatization of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections. b s t r a c tPeri-prosthetic infections are notoriously difficult to treat as the biomaterial implant is ideal for bacterial adhesion and biofilm formation, resulting in decreased antibiotic sensitivity. Previously, we reported that vancomycin covalently attached to a Ti alloy surface (Vanc-Ti) could prevent bacterial colonization. Herein we examine the effect of this Vanc-Ti surface on Staphylococci epidermidis, a Gram-positive organism prevalent in orthopaedic infections. By direct colony counting and fluorescent visualization of live bacteria, S. epidermidis colonization was significantly inhibited on Vanc-Ti implants. In contrast, the gram-negative organism Escherichia coli readily colonized the Vanc-Ti rod, suggesting retention of antibiotic specificity. By histochemical and SEM analysis, Vanc-Ti prevented S. epidermidis biofilm formation, even in the presence of serum. Furthermore, when challenged multiple times with S. epidermidis, Vanc-Ti rods resisted bacterial colonization. Finally, when S. epidermidis was continuously cultured in the presence of Vanc-Ti, the bacteria maintained a Vanc sensitivity equivalent to the parent strain. These findings indicate that antibiotic derivatization of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections.

Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self‐Antimicrobial and Immunomodulatory Properties

“…Many conventional antibiotics like gentamicin, vancomycin, and chlorohexidine have been applied on titanium surfaces as strategies to prevent peri-implantitis. [ 5,6 ] However, the emergence of multidrug resistant bacterium like methicillin-resistant S. aureus (MRSA) has critically challenged the use of conventional antibiotics. [ 7 ] A promising alternative to conventional antibiotics is the use of short cationic antimicrobial peptides (AMPs).…”

Bases moleculares de la infección asociada a implantes ortopédicos

“…Las propiedades de la superficie, principalmente la hidrofobicidad y la presencia de cargas, juegan un rol en la adhesión y proliferación bacteriana inicial 7 . La superficie del implante ortopédico, luego de ser colocada en el medio interno, acumula proteínas séricas y de la matriz extracelular (colágeno, fibronectina, fibrinógeno, vitronectina, sialoproteína ósea, elastina y trombospondina) que promueven la adherencia y colonización bacteriana, siendo éste un paso crítico en el desarrollo de las infecciones asociadas a implante ortopédico 5,29,31 . La interacción directa entre la bacteria y la superficie juega un rol crítico en las etapas tempranas del proceso de adherencia.…”

“…El "patrón de oro" para liberación de antimicrobianos de forma local es el cemento óseo impregnado con antibacterianos (polimetilmetacrilato: PMMA). El uso de antibacterianos cargados en el PMMA permite la liberación de altas concentraciones de antibacterianos en el área afectada sin causar toxicidad sistémica 31 . El uso de cemento con antibacterianos ha demostrado ser útil de forma precoz.…”

“…El uso de vancomicina covalentemente unida a una aleación de titanio, previene la colonización y formación de biopelículas por S. epidermidis, pero su biocompatibilidad ha sido cuestionada 31 . A diferencia de vancomicina, el uso de nano partículas de sílice liberadoras de óxido nítrico (NO) in vitro para destruir células protegidas por biopelícula (P. aeruginosa, E. coli, S. aureus, S. epidermidis y Candida albicans) demostró más de 99% de efectividad.…”

Antimicrobial and osteogenic effect of Ag-implanted titanium with a nanostructured surface

“…Therefore, strategies involving the delivery or incorporation of antibiotics such as gentamicin and vancomycin on some titanium implants have been tried to reduce infections. 4,5 With increasing concerns over antibiotic-resistant pathogens, however, non-conventional antibiotics have been developed in an attempt to avoid these problems without compromising the treatment of infection. Silver is effective against a broad spectrum of bacterial and fungal species, including strains that are resistant to antibiotics.…”