Lysostaphin-Coated Mesh Prevents Staphylococcal Infection and Significantly Improves Survival in a Contaminated Surgical Field

Abstract

Mesh and wound infections during hernia repair are predominantly caused by Staphylococcus aureus. Human acellular dermis (HAD) is known to lose its integrity in the face of large bacterial loads. The goal of this study was to determine if lysostaphin (LS), a naturally occurring anti-Staphylococcal protein, can protect HAD mesh from S. aureus infection. HAD samples, 3 cm X 3 cm, were implanted in the onlay fashion on the anterior abdominal wall of rats (n = 75). Subjects were grouped based on presence of antimicrobial bound to HAD (none or LS) and presence of S. aureus inoculum (sterile, 106, 108 CFU). At 60 days, meshes were explanted, and bacterial growth, histology, and mesh tensile strength were examined. None of the controls receiving bacterial inoculation without LS survived to 60 days. All LS-HAD sterile and LS-106 animals survived to explantation. The LS-HAD 108 group had a mortality rate of 50 per cent. All surviving LS-treated animals (n = 25) had negative wound and mesh cultures. Blinded gross and histologic evaluation and measured tensile strengths between all LS groups were comparable. Animals implanted with LS-HAD had a dramatically improved rate of survival. All animals surviving to 60 days had completely cleared S. aureus from their wounds with maintenance of mesh integrity and tensile strength. These findings strongly suggest the clinical use of LS-treated mesh in contaminated fields may translate into a more durable hernia repair.

Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio‐Functionality to Meshes

“…For example, lysostaphin is a staphylococcal endopeptidase that exhibits a CMI 90 against MRSA up to 1000 times lower than conventional drugs, such as vancomycin and has the advantage of lysing S. aureu s membrane by microperforation on both dividing cells and quiescent biofilms. Synthetic and biological meshes have been loaded with lysostaphin (during an immersion step) and have demonstrated in vitro a direct concentration‐dependent inhibition of S. aureus . Satisfactory antibiofilm protection of meshes coated with a solution of lysostaphin at 100 μg/mL was observed in both in vitro and in vivo experiments (in a rat infected model), without having a negative impact on the tissue integration and the mechanical integrity of the implants …”

“…Synthetic and biological meshes have been loaded with lysostaphin (during an immersion step) and have demonstrated in vitro a direct concentration‐dependent inhibition of S. aureus . Satisfactory antibiofilm protection of meshes coated with a solution of lysostaphin at 100 μg/mL was observed in both in vitro and in vivo experiments (in a rat infected model), without having a negative impact on the tissue integration and the mechanical integrity of the implants …”

What would surgeons like from materials scientists?

“…Many surgeons irrigate wounds with antibiotics or antiseptics to reduce bacterial concentrations . Strategies to prevent bacterial adhesion to implants have included antibiotic and triclosan coatings, antistaphylococal agents, and agents to reduce bacterial adhesion such as chitosan and silver nanoparticles . Some caution must be used when introducing agents into open wounds since they can interfere with healing .…”

“…Some caution must be used when introducing agents into open wounds since they can interfere with healing . Wide spread use of antibiotics and triclosan may also result in bacterial resistance, allergic reactions, or possible untoward endocrine, metabolic, or environmental effects Above all, the material must fulfill its intended function.…”

“…All synthetic meshes currently on the market are subject to infection, and although mesh can sometimes be salvaged after infection, they often need to be removed. The search for infection resistant mesh continues …”