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

Abstract

Background

Clinical 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.

Methods

PLGA 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.

Results

The 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.

Conclusions

In vitro and in vivo analyses showed that the use of biodegradable PLGA vancomycin beads successfully eradicated S. aureus infection in damaged bone.