Preventing Implant-Associated Infections by Silver Coating

Antimicrob Agents Chemother. 2016 Mar 25;60(4):2467-75. doi: 10.1128/AAC.02934-15. Print 2016 Apr.

Abstract

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity againstStaphylococcus epidermidisandStaphylococcus aureusin an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10(6)CFU ofS. epidermidisper cage. InS. aureusinfections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not preventS. aureusinfections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistantS. aureusinfections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 μg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Cell Survival / drug effects
  • Coated Materials, Biocompatible / pharmacology*
  • Daptomycin / pharmacology
  • Dental Alloys / pharmacology*
  • Drug Liberation
  • Female
  • Kinetics
  • Leukocytes / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Prostheses and Implants / microbiology*
  • Silver / pharmacokinetics
  • Silver / pharmacology*
  • Skin
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / growth & development
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Coated Materials, Biocompatible
  • Dental Alloys
  • titanium-niobium-aluminum alloy
  • Silver
  • Vancomycin
  • Daptomycin

Grants and funding

This work was supported by the Stiftung Forschung Infektionskrankheiten.