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

Steve W N Ueng,I-Chun Wang,Cheng-Fen Lai,Song-Shu Lin,Li-Jen Yuan,Shih-Jung Liu,Err-Cheng Chan,Chuen-Yung Yang,Sheng-Chieh Chan,Ru-Chin Cheng

doi:10.1186/s13018-016-0386-x

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.

Highlights

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
We evaluated the release of vancomycin from PLGA vancomycin beads and examined the relative activity of the released antibiotics in vitro
The diameter of the sample inhibition zone ranged from 6.5 to 10 mm, which was equivalent to 12.5–100 % relative activity in the bacterial inhibition test

Summary

Introduction

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. 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. Despite advances in surgical techniques and the availability of newly developed antibiotics, bone infections after surgical procedures and trauma continue to be a difficult problem for surgeons [1, 2]. Operative debridement and antibiotic therapy are preferred treatments for bone infection [3]. Intravenous route of antibiotic injection produces adequate antibiotic concentration in the blood, recurrence of infection, the high cost of the antibiotics, and poor patient compliance are still problems. Antibiotic-impregnated PMMA beads provide a high local concentration of the drug and have advantages over intravenous injection in that the beads yield fewer systemic complications and allergic reactions. PMMA beads require a second operation for removal after prolonged implantation [1, 9]

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