Efficacy of vancomycin-releasing biodegradable poly(lactide-co-glycolide) antibiotics beads for treatment of experimental bone infection due to Staphylococcus aureus.
BACKGROUND
Clinical experience and animal studies have suggested that positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose ((18)F-FDG) may be promising for imaging of bone infections. In this study, we aimed to establish the accuracy of (18)F-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 (18)F-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. (18)F-FDG PET results showed that uncomplicated bone healing was associated with a temporary increase in (18)F-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 (18)F-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 (18)F-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.
Department of Orthopaedic, Chang Gung Memorial Hospital, Linkou, Taiwan. wenneng@adm.cgmh.org.tw.|Bone and Joint Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan. wenneng@adm.cgmh.org.tw.|Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, No 5, Fu-Hsing Street 333, Kweishan, Taoyuan, Taiwan. wenneng@adm.cgmh.org.tw.
Steve W N
SW
Ueng
Department of Orthopaedic, Chang Gung Memorial Hospital, Linkou, Taiwan.
Song-Shu
SS
Lin
Department of Orthopaedic, Chang Gung Memorial Hospital, Keelung, Taiwan.
I-Chun
IC
Wang
Department of Orthopaedic, Chang Gung Memorial Hospital, Linkou, Taiwan.
Chuen-Yung
CY
Yang
Department of Nuclear Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
Ru-Chin
RC
Cheng
Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan.
Shih-Jung
SJ
Liu
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
Err-Cheng
EC
Chan
Laboratory Animal Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
Cheng-Fen
CF
Lai
Department of Orthopaedic, Chang Gung Memorial Hospital, Linkou, Taiwan.
Li-Jen
LJ
Yuan
Department of Nuclear Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
Sheng-Chieh
SC
Chan
D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants; D019788:Fluorodeoxyglucose F18; D008297:Male; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000382:microbiology; D011098:Polyglactin 910; D000072078:Positron Emission Tomography Computed Tomography; D049268:Positron-Emission Tomography; D011817:Rabbits; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004343:Drug Implants; D019788:Fluorodeoxyglucose F18; D011098:Polyglactin 910; D014640:Vancomycin
18F-FDG PET; Bone infection; PLGA; Vancomycin