Efficacy of vancomycin-releasing biodegradable poly(lactide-co-glycolide) antibiotics beads for treatment of experimental bone infection due to Staphylococcus aureus

Abstract

BackgroundClinical experience and animal studies have suggested that positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose (18F-FDG) may be promising for imaging of bone infections. In this study, we aimed to establish the accuracy of 18F-FDG PET scanning for monitoring the response to poly(lactide-co-glycolide) (PLGA) vancomycin beads for treatment of bone infection.MethodsPLGA was mixed with vancomycin and hot-compress molded to form antibiotic beads. In vitro, elution assays and bacterial inhibition tests were employed to characterize the released antibiotics. In vivo, cylindrical cavities were made in six adult male New Zealand white rabbits, and Staphylococcus aureus or saline was injected into the cavity to create a bone infection. After 2 weeks, the infection was confirmed by bacterial cultures, and the defect was filled with PLGA vancomycin beads. The treatment response was monitored by 18F-FDG PET.ResultsThe biodegradable beads released high concentrations of vancomycin (well above the breakpoint sensitivity concentration) for treatment of bone infection. In bacterial inhibition tests, the diameter of the sample inhibition zone ranged from 6.5 to 10 mm, which was equivalent to 12.5–100 % relative activity. 18F-FDG PET results showed that uncomplicated bone healing was associated with a temporary increase in 18F-FDG uptake at 2 weeks, with return to near baseline at 6 weeks. In the infected animals, localized infection resulted in intense continuous uptake of 18F-FDG, which was higher than that in uncomplicated healing bones. Bone infection was confirmed with positive bacterial cultures. In vancomycin-treated animals, data showed rapidly decreasing amounts of 18F-FDG uptake after treatment.ConclusionsIn vitro and in vivo analyses showed that the use of biodegradable PLGA vancomycin beads successfully eradicated S. aureus infection in damaged bone.

Multifunctional Antibiotic and Zinc Containing Mesoporous Bioactive Glass Scaffolds to Fight Against Bone Infection

“…7) and planktonic growth experiments (fig. 8) where it was possible to confirm the antibacterial efficiency of same antibiotics for same strain [41][42][43][44][45]. When biofilms were in contact with the unloaded 4ZN-GE scaffolds a partial biofilm destruction was found in both strains which show zinc antibacterial effect by itself.…”

“…S. aureus 4ZN-GE scaffolds were loaded with LEVO, VANCO and RIFAM because their referenced effectiveness against S. aureus (Fig. 7.1-3) [41][42][43]. The antibiotic loaded scaffolds were named as 4ZN-GE-L, 4ZN-GE-V and 4ZN-GE-R, respectively.…”

Recent advances in the local antibiotics delivery systems for management of osteomyelitis

“…The composite system of the two polymers revealed adequate osteogenic differentiation of mesenchymal stem cells in a rabbit model (Ueng et al., 2011 ). Further in-vitro and in-vivo studies applying the biodegradable PLGA-vancomycin beads confirmed their success in eradicating the induced infection in the damaged bone of rabbits model (Ueng et al., 2016 ).…”

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

“…These technologies include 3D-printing, bacterial genomic sequencing and microbiome profiling, and real-time in vivo imaging modalities. [33][34][35][36][37]134 These technologies have enabled the development of species-specific reproducible implants, 34,134 incorporation of patient risk factors for implant infection into the model (e.g., diabetes, gut microbiome constituents), 32,33 and real-time minimally invasive tracking of infection and inflammation in vivo. 37 Furthermore, the emergence of stimuli-responsive antimicrobial materials (e.g., responsive to temperature, magnetic/electric fields, microwaves, etc.)…”