Evaluation of the Antimicrobial Activity of Lysostaphin-Coated Hernia Repair Meshes

Abstract

Bacterial infections by antibiotic-resistant Staphylococcus aureus strains are among the most common postoperative complications in surgical hernia repair with synthetic mesh. Surface coating of medical devices/ implants using antibacterial peptides and enzymes has recently emerged as a potentially effective method for preventing infections. The objective of this study was to evaluate the in vitro antimicrobial activity of hernia repair meshes coated by the antimicrobial enzyme lysostaphin at different initial concentrations. Lysostaphin was adsorbed on pieces of polypropylene (Ultrapro) mesh with binding yields of ϳ10 to 40% at different coating concentrations of between 10 and 500 g/ml. Leaching of enzyme from the surface of all the samples was studied in 2% (wt/vol) bovine serum albumin in phosphate-buffered saline buffer at 37°C, and it was found that less than 3% of adsorbed enzyme desorbed from the surface after 24 h of incubation. Studies of antibacterial activity against a cell suspension of S. aureus were performed using turbidity assay and demonstrated that the small amount of enzyme leaching from the mesh surface contributes to the lytic activity of the lysostaphincoated samples. Colony counting data from the broth count (model for bacteria in wound fluid) and wash count (model for colonized bacteria) for the enzyme-coated samples showed significantly decreased numbers of CFU compared to uncoated samples (P < 0.05). A pilot in vivo study showed a dose-dependent efficacy of lysostaphincoated meshes in a rat model of S. aureus infection. The antimicrobial activity of the lysostaphin-coated meshes suggests that such enzyme-leaching surfaces could be efficient at actively resisting initial bacterial adhesion and preventing subsequent colonization of hernia repair meshes.The development of an incisional hernia is a common complication after abdominal surgery, which results in 90,000 ventral hernia repair surgeries per year in the United States (25). The implantation of a prosthetic mesh is a well-established procedure for reconstructing or reinforcing the abdominal wall and has been shown to decrease the rate of hernia recurrence (7,18,24). However, one of the most common problems associated with the use of prosthetic meshes is bacterial infection. The incidence rate for mesh-related infection has been reported to vary between 1% and 18% in different clinical studies (9,16,17).Staphylococcus aureus is a prevalent microorganism of skin flora; as a consequence, it is responsible for over 90% of surgical site infections as well as mesh related infections (2, 6, 10). Mesh infection is associated with significant morbidity and is increased considerably in patients with diabetes, immunosuppression, and obesity. Surgical site and implant contamination usually happens at the time of surgery and in the early postoperative period. Current conventional infection-prevention therapies have not been successful in reducing the rate of surgical site infection (8,26). Furthermore, operative technique refinements have led t...

The Addition of Lysostaphin Dramatically Improves Survival, Protects Porcine Biomesh from Infection, and Improves Graft Tensile Shear Strength

“…Kokai-Kun et al demonstrated that lysostaphin has the ability to eradicate biofilm-protected S. aureus from surfaces in vitro [22]. Satishkumar et al examined antimicrobial properties of lysostaphin bound to mesh in vitro, reporting that such enzyme leaching surfaces actively resist bacterial adhesion and prevent subsequent colonization of hernia meshes [23]. Schaffner et al used lysostaphin intravenously in mice challenged with a S. aureus inoculum, showing that the lysostaphin recipients had a significantly higher survival than animals treated with oxacillin or the untreated controls [24].…”

Dispersion of Silver Nanoparticles into Polymer Matrix Dry Adhesives to Achieve Antibacterial Properties, Increased Adhesion, and Optical Absorption

“…Other studies monitoring the antibacterial activity of solids with silver or other antibiotics have recorded a wide range of antibacterial efficacies, from 1 log-unit reduction for 24 h exposure [15] to 3 log-units reduction for 5 h exposure [30] and 2 log-units reduction for 30 min exposure.…”

Hydrogen/Deuterium Exchange Mass Spectrometry and Site-Directed Disulfide Cross-Linking Suggest an Important Dynamic Interface between the Two Lysostaphin Domains

“…Lysostaphin has been extensively studied as a therapeutic agent, with either topical or systemic administration, for the treatment of S. aureus infections (8)(9)(10)(11)(12)(13). Now, recombinant lysostaphin is being effectively developed as a new topical antibacterial agent to control S. aureus infections in burn wounds in China (phase III clinical trials).…”

“…Previous in vitro and in vivo studies have shown that lysostaphin is an effective therapeutic agent against antibiotic-resistant S. aureus (8)(9)(10)(11)(12)(13)(14). For example, lysostaphin, given as a single dose (100 mg/kg) or twice daily (30 mg/kg) for 3 days, has been shown to be more effective than vancomycin (30 mg/kg, twice daily for 3 days) for the treatment of experimental aortic valve endocarditis caused by vancomycin-intermediate S. aureus in rabbits (15).…”