Microbiological and pharmacological tests on new antibiotic‐loaded PMMA‐based composites for the treatment of osteomyelitis

Abstract

Local antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with btricalcium phosphate (P-TCP) and BaSO 4 or only with BaSO 4 (P-BaSO 4 ), and soaked in a solution of gentamicin (G) and vancomycin (V) was studied. Nails were implanted into the intramedullary cavity of healthy and osteomyelitic femurs to study the resolution of infection and to quantify the antibiotic penetration into bone by microbiological, pharmacological, and histological tests. A significant progression of osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria were found in animals treated with antibiotic-loaded nails as confirmed by microbiology and histology (Smeltzer score). The release of both antibiotics from composites was high and prompt both in healthy and infected bone; the amount of V was higher than that of G in all bone samples. Antibiotics of both composites were still present in bone 3 weeks after nail implantation. The P-BaSO4 composite released a lower amount of antibiotics than did P-TCP. The G-V combination in vivo exerted a synergistic bactericidal effect, which was confirmed by microbiological, histological, and clinical results (no infection). These new porous PMMA composites, soaked in G-V solution in the operating room, might be an effective and useful drug delivery system for osteomyelitis treatment. ß

Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

“…These factors emphasize the need to develop methods to enhance delivery of vancomycin to bone in the treatment of osteomyelitis. One way to accomplish this is to employ local antibiotic delivery, which while useful suffers from inherent limitations, not the least being the ability to gain direct access to the infection site (8)(9)(10)(11)(12)(13)(14)(15)(16). Thus, one of the major challenges to improve therapeutic outcomes for osteomyelitis patients is to develop methods for the systemic deliv-ery of vancomycin, and potentially other antibiotics, in sufficient concentrations to achieve the desired therapeutic effect.…”

Polymicrobial Biofilm Inhibition Effects of Acetate‐Buffered Chitosan Sponge Delivery Device

“…Optimal loading concentrations for PMMA may be determined through modeling and rational selection, although slow release is still a concern requiring porosity inducing additives to improve elution of certain antibiotics . The duration of antibiotic release observed in vitro from sponges was relatively short compared with duration of up to 36 weeks of release from PMMA . Comparison of in vivo results in this model between PMMA and chitosan sponges cannot be made, since nondegradable PMMA implants have not been evaluated in this soft tissue defect and are typically evaluated in larger orthopedic defect models .…”

“…The two most commonly used local delivery devices in musculoskeletal clinical practice, polymethylmethacrylate (PMMA) beads and calcium sulfate, have demonstrated efficacy in release of antibiotic and inhibition of bacterial growth . PMMA is not degradable and is primarily used for treatment after infection develops, particularly when there is a need for material maintenance of space prior to reconstruction .…”

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm

“…Antiinfective biomaterials are increasingly used as an adjunctive strategy to prevent implanted biomaterial infections and to inhibit biofilm-forming microorganisms [13,27,44,49,55,63,64]. Commonly used local antibiotic delivery systems range from antibiotic-loaded bone cement to calcium-based drug delivery systems to sprinkling antibiotics within the wound site [8,24,40,42]. Recent developments have been focused on degradable and customizable local delivery strategies to ensure coverage of the wound, effective antibiotic elution, and minimization of secondary procedures [15,30,60].…”