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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2016

Open Access 01-12-2016 | Research article

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

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

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2016

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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.
Literature
1.
Ueng SWN, Wei FC, Shih CH, et al. Management of large infected tibial defect with antibiotic beads local therapy and staged fibular osteoseptocutaneous free transfer. J Trauma. 1997;43:268–74.CrossRefPubMed
2.
Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III open fracture. J Trauma. 1984;24:742–6.CrossRefPubMed
3.
Mader JT, Calhoun J, Cobos J. In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads. Antimicrob Agents Chemother. 1997;41:415–8.PubMedPubMedCentral
4.
Patzakis MJ, Mazur K, Wilkins J, et al. Septopal beads and autogenous bone grafting for bone defects in patients with chronic osteomyelitis. Clin Orthop Relat Res. 1993;295:112–8.PubMed
5.
Cierny III G, Mader JT. A clinical staging system for adult osteomyelitis. Contemp Orthop. 1985;10:17–37.
6.
Greene N, Holtom PD, Warren CA, et al. In vitro elution of tobramycin and vancomycin PMMA beds and spacers from Simplex and Palacos. Am J Orthop. 1998;27:201–5.PubMed
7.
Holtom PD, Warren CA, Greene NW, et al. Relation of surface area to in vitro elution characteristics of vancomycin-impregnated PMMA spacers. Am J Orthop. 1998;27:207–10.PubMed
8.
Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg. 1970;11:511–5.
9.
Henry SL, Seligson D, Mangino P, et al. Antibiotic-impregnated beads. Part I: bead implantation versus systemic therapy. Orthop Rev. 1991;20:242–7.PubMed
10.
Ueng SWN, Lee MS, Lin SS, et al. Development of a biodegradable alginate carrier system for antibiotics and bone cells. J Orthop Res. 2007;25:62–72.CrossRefPubMed
11.
Lin SS, Ueng SW, Liu SJ, et al. Development of a biodegradable antibiotic delivery system. Clin Orthop. 1999;362:240–50.CrossRefPubMed
12.
Liu SJ, Ueng SW, Chan EC, et al. In vitro elution of vancomycin from biodegradable beads. J Biomed Mater Res. 1999;48:613–20.CrossRefPubMed
13.
Shinto Y, Uchida A, Korkusaz F, et al. Calcium hydroxyapatite ceramic used as a drug delivery system for antibiotics. J Bone Joint Surg. 1992;74B:600–4.
14.
Garvin KL, Miyano JA, Robinson D, et al. Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis: a canine model. J Bone Joint Surg. 1994;76A:1500–6.
15.
Ueng SWN, Yuan LJ, Lee N, et al. In vivo study of hot compressing molded 50:50 poly (DL-lactide-co-glycolide) antibiotic beads in rabbits. J Orthop Res. 2002;20:654–66.CrossRefPubMed
16.
Gemmel F, Van den Wyngaert H, Love C, et al. Prosthetic joint infections: radionuclide state-of-the-art imaging. Eur J Nucl Med Mol Imaging. 2012;39:892–909.CrossRefPubMed
17.
van der Bruggen W, Bleeker-Rovers CP, Boerman OC, et al. PET and SPECT in osteomyelitis and prosthetic bone and joint infections: a systematic review. Semin Nucl Med. 2010;40:3–15.CrossRefPubMed
18.
Ota K, Oishia N, Ito K, et al. Effects of imaging modalities, brain atlases and feature selection on prediction of Alzheimer’s disease. J Neurosci Methods. 2015;256:168–83.CrossRefPubMed
19.
Chrapko B, Chrapko M, Nocuń A, et al. Role of 18F-FDG PET/CT in the diagnosis of inflammatory and infectious vascular disease. Nucl Med Rev. 2016;19(1):28–36.CrossRef
20.
Scialpi M, Palumbo I, Gravante S, et al. Multi-detector row CT fusion imaging in oncologic patients: preliminary results. Radiology. 2016;278:873–80.CrossRefPubMed
21.
Fathinul F, Nordin A. 18F-FDG PET/CT as a potential valuable adjunct to MRI in characterising the Brodie's abscess. Biomed Imaging Interv J. 2010;6:e26.CrossRefPubMedPubMedCentral
22.
Beslic N, Heber D, Walter Lipp R, et al. Metabolic pattern of asymptomatic hip prosthesis by 18F-FDG–positron-emission-tomography. Iran J Radiol. 2015;12, e11204.PubMedPubMedCentral
23.
24.
Shemesh S, Kosashvili Y, Groshar D, et al. The value of 18-FDG PET/CT in the diagnosis and management of implant-related infections of the tibia: a case series. Injury Int J Care Injured. 2015;46:1377–82.CrossRef
25.
Koort JK, Mäkinen TJ, Suokas E, et al. Efficacy of ciprofloxacin-releasing bioabsorbable osteoconductive bone defect filler for treatment of experimental osteomyelitis due to Staphylococcus aureus. Antimicrob Agents Chemother. 2005;49:1502–8.CrossRefPubMedPubMedCentral
26.
Sugawara Y, Gutowski TD, Fisher SJ, et al. Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA. Eur J Nucl Med. 1999;26:333–41.CrossRefPubMed
27.
Brown TL, Spencer HJ, Beenken KE, et al. Evaluation of dynamic [18F]-FDG-PET imaging for the detection of acute post-surgical bone infection. PLoS One. 2012;7, e41863.CrossRefPubMedPubMedCentral
28.
Koort JK, Ma¨kinen TJ, Knuuti J, et al. Comparative 18F-FDG PET of experimental Staphylococcus aureus osteomyelitis and normal bone healing. J Nucl Med. 2004;45:1406–11.PubMed
29.
Odekerken JC, Walenkamp GH, Brans BT, et al. The longitudinal assessment of osteomyelitis development by molecular imaging in a rabbit model. Biomed Res Int. 2014;24652:2014.
30.
Haddad FS, Muirhead-Allwood SK, Manktelow AR, et al. Two stage uncemented revision hip arthroplasty for infection. J Bone Jt Surg. 2000;82b:689–94.CrossRef
31.
Walcott BP, Redjal N, Coumans JV. Infection following operations on the central nervous system: deconstructing the myth of the sterile field. Neurosurg Focu. 2012;33, E8.CrossRef
32.
Calhoun JH, Mader JT. Treatment of osteomyelitis with a biodegradable antibiotic implant. Clin Ortho. 1997;341:206–14.CrossRef
33.
Garvin KL, Miyano JA, Robinson D, et al. Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis: a canine model. J Bone Joint Surg Am. 1994;76:1500–6.PubMed
34.
Zhang X, Wyss UP, Pichora D, Goosen MF. Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties. J Pharm Pharmacol. 1994;46:718–24.CrossRefPubMed
35.
Jacob E, Setterstrom JA, Bach DE, et al. Evaluation of biodegradable ampicillin anhydrate microcapsules for local treatment of experimental staphylococcal osteomyelitis. Clin Ortho. 1991;267:237–44.
36.
De Winter F, Vogelaers D, Gemmel F, et al. Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in clinical infectious diseases. Eur J Clin Microbiol Infect Dis. 2002;21:247–57.CrossRefPubMed
37.
Zhuang HM, Alavi A. 18-Fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med. 2002;32:47–59.CrossRefPubMed
38.
Paik JY, Lee KH, Choe YS, et al. Augmented 18F-FDG uptake in activated monocytes occurs during the priming process and involves tyrosine kinases and protein kinase C. J Nucl Med. 2004;45:124–8.PubMed
39.
Mochizuki T, Tsukamoto E, Kuge Y, et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med. 2001;42:1551–5.PubMed
40.
Pauwels EKJ, Ribeiro MJ, Stoot JH, et al. FDG accumulation and tumor biology. Nucl Med Biol. 1998;25:317–22.CrossRefPubMed
41.
Meyer M, Gast T, Raja S, et al. Increased F-18 FDG accumulation in an acute fracture. Clin Nucl Med. 1994;19:13–4.CrossRefPubMed
42.
Kubota R, Yamada S, Kubota K, et al. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissue studied by microautoradiography. J Nucl Med. 1992;33:1972–80.PubMed
43.
Chatziioannou S, Papamichos O, Gamaletsou MN, et al. 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan for monitoring the therapeutic response in experimental Staphylococcus aureus foreign-body osteomyelitis. J Orthop Surg Res. 2015;10:132.CrossRefPubMedPubMedCentral
44.
Lankinen P, Lehtimäki K, Hakanen AJ, et al. A comparative 18F-FDG PET/CT imaging of experimental Staphylococcus aureus osteomyelitis and Staphylococcus epidermidis foreign-body-associated infection in the rabbit tibia. EJNMMI Res. 2012;2:41.CrossRefPubMedPubMedCentral
45.
Zhuang H, Duarte PS, Pourdehnad M, et al. The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants. J Nuc Med. 2001;42:44–8.
Metadata
Title
Efficacy of vancomycin-releasing biodegradable poly(lactide-co-glycolide) antibiotics beads for treatment of experimental bone infection due to Staphylococcus aureus
Authors
Steve W. N. Ueng
Song-Shu Lin
I-Chun Wang
Chuen-Yung Yang
Ru-Chin Cheng
Shih-Jung Liu
Err-Cheng Chan
Cheng-Fen Lai
Li-Jen Yuan
Sheng-Chieh Chan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2016
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-016-0386-x

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