RESULTS OF THE FOSFOMYCIN APPLICATION FOR THE IMPREGNATION OF BONE REPLACEMENT MATERIALS IN THE TREATMENT OF CHRONIC OSTEOMYELITIS
- 作者: Konev V.A.1, Bozhkova S.A.1, Netylko G.I.1, Afanasiev A.V.1, Rumakin V.P.1, Polyakova E.M.1, Rukina A.N.1, Parfeev D.G.1
-
隶属关系:
- Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
- 期: 卷 22, 编号 2 (2016)
- 页面: 43-56
- 栏目: Theoretical and experimental studies
- ##submission.dateSubmitted##: 16.09.2016
- ##submission.dateAccepted##: 16.09.2016
- ##submission.datePublished##: 16.09.2016
- URL: https://journal.rniito.org/jour/article/view/157
- DOI: https://doi.org/10.21823/2311-2905-2016-0-2-43-56
- ID: 157
如何引用文章
全文:
详细
Aim – to evaluate in the experimental study in vitro the duration of antimicrobial activity of fosfomycin-impregnated bone cement and to study the dynamics of radiological and morphological changes depending on the local antibiotic therapy in two-stage treatment of chronic osteomyelitis in rabbits.
Materials and methods. Duration of antimicrobial activity of bone cement (depuy cmw1 gentamicin) with fosfomycin in vitro was studied in comparison to cements with vancomycin and controls without additional antibiotics. Presence of the lysis zone of bacterial cultures was evaluated (Staphylococcus aureus ATCC6538 and ATCC33591, Klebsiella pneumoniae ATCC33495 and Escherichia coli ATCC25922) after application of 10 μl of the solution, collected from the cement samples after incubation for 24 hours. For the in vivo experiment, Chinchilla rabbits (n = 20) with local osteomyelitis of the tibia underwent two-stage treatment where substitution of the bone defect at stage I was performed with PMMA and stage II – with the bioresorbable material based on hydroxyapatite and triclacium phosphate (ReproBone). In an experience group (n = 10) before setting osteoreplacement materials with fosfomycin (group FOSFO), and by control (n = 10) – vancomycin (group VANCO). X-ray imaging was performed on the 1st and 21st day after installation of the cement spacer, and 45th day after substitution of the spacer with the bioresorbable material. Microbiological analysis of the samples was performed intraoperatively and on the 7th, 14th day after each stage. Histological study was conducted in both groups on the 14th, 21th day after stage I and 45th day after stage II of the treatment.
Results. Maximal duration of antimicrobial activity in vitro was observed in samples of PMMA with fosfomycin whereas minimal – in control samples of gentamicin-based bone cement. Relief of the infection was attained in all animals while application of fosfomycin resulted in a more rapid elimination of the bacteria. Reaction of the adjacent tissue to the implanted material and results of X-ray imaging in both groups did not differ significantly. Long duration of the broad-spectrum antimicrobial activity of the bone cement with fosfomycin with the comparable perifocal reaction in vivo necessitates further study of the use of this antibiotic in bioresorbable materials for the treatment of osteomyelitis in clinical practice.
作者简介
V. Konev
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
编辑信件的主要联系方式.
Email: vladimirkonev24@mail.ru
researcher of the research Department of experimental morphology, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦S. Bozhkova
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
head of the research Department of prevention and treatment of wound infection and Department of clinical pharmacology, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦G. Netylko
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
head of the research Department of experimental morphology, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦A. Afanasiev
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
orthopedic surgeon and laboratory researcher of the research Department of prevention and treatment of wound infection, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦V. Rumakin
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
head of the pathology Department, Vreden Russian Research Institute of Traumatology and Orthopedics 俄罗斯联邦
E. Polyakova
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
senior researcher of the research Department of prevention and treatment of wound infection, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦A. Rukina
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
clinical bacteriologist and junior researcher of the research Department of prevention and treatment of wound infection, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦D. Parfeev
Vreden Russian Research Institute of Traumatology and Orthopedics, ul. Ak. Baykova, 8, St. Petersburg, Russia, 195427
Email: fake@neicon.ru
head of trauma and orthopedic Department N 1, Vreden Russian Research Institute of Traumatology and Orthopedics
俄罗斯联邦参考
- Баринов С.М., Комлев В.С. Биокерамика на основе фосфатов кальция. М.: Наука; 2005. 204 с.
- Божкова С.А., Тихилов Р.М., Краснова М.В., Рукина А.Н. Ортопедическая имплантат- ассоциированная инфекция: ведущие возбудители, локальная резистентность и рекомендации по антибактериальной терапии. Травматология и ортопедия России. 2013; (4):5-15.
- Божкова С.А., Новокшонова А.А., Конев В.А. Современные возможности локальной антибиотикотерапии перипротезной инфекции и остеомиелита (обзор литературы). Травматология и ортопедия России. 2015; (3):92-107.
- Гринев М.В. Остеомиелит. Л : Медицина; 1977. 152 с.
- Клюшин Н.М, Науменко З.С., Розова Л.В., Леончук Д.С. Микрофлора хронического остеомиелита плечевой кости. Гений ортопедии. 2014; (3):57-59.
- Корж Н.А., Кладченко Л.А, Малышкина С.В. и др. Имплантационные материалы и остеогенез. Ортопедия,травматология и протезирование. 2005; (4):118-127.
- Линник, С.А., Ромашов П.П., Новоселов К.А. Применение препарата ОSTEOSET для заполнения костных полостей. Травматология и ортопедия России. 2009; (3):155-156.
- Лунева С.Н. Влияние состава биокомпозиционных материалов, имплантированных в дырчатые дефекты метафиза, на репаративную регенерацию и менерализацию костной ткани. Бюллетень экспериментальной биологии и медицины. 2013; (8):255- 259.
- Мамонов В.Е., Чемис А.Г., Дризе Н.И., Проскурина И.В., Кряжков И.И., Комлев B.C. Исследование in vivo трехкомпонентного резорбируемого кальцийфосфатного цемента на основе трикальцийфосфата. Вестник травматологии и ортопедии им. Н.Н. Приорова. 2014; (1):72-77.
- Материалы международной согласительной конференции по перипротезной инфекции. Перевод с англ. под ред. Р.М. Тихилова. СПб.: РНИИТО им. Р.Р. Вредена; 2013. 355 с.
- П утляев В.И., Сафронова Т.В. Новое поколение кальций-фосфатных биоматериалов: роль фазового и химического составов. Стекло и керамика. 2006; (3):30-33.
- Сафина Н., Сафронова Т., Баринов С. Биокерамика в медицине. Стекло и керамика. 2007; (2):34-36.
- Barinov S.M., Komlev V.S. Calcium phosphate bone cements. Inorganic Mater. 2011; 47(13):1470-1485. Available at: http://link.springer.com/article/10.1134/S0020168511130024#/page-1
- Bohner М. Design of ceramic-based cements and putties for bone graft substitution. Eur Cell Mater. 2010; 20:1-12.
- Campana V., Milano G., Pagano E., Barba M., Cicione C., Salonna G., Lattanzi W. Bone substitutes in orthopedic surgery: from basic science to clinical practice. J Mater Sci Mater Med. 2014; 25:2445-2461.
- Dorozhkin S.V. Calcium orthophosphate cements and concretes. Materials. 2009; 2: 221- 291. Available at: http://www.mdpi.com/1996-1944/2/1/221
- Dorozhkin S.V. Self-setting calcium orthophosphate formulations. J Funct Biomater. 2013; 4(4):209-311. doi: 10.3390/jfb4040209.
- Ensing G.T., Van Horn J.R., van der Mei H.C., Busscher H.J., Neut D. Copal bone cement is more effective in prevening bioform formation than Palacos R-G. Clin Orthop Relat Res. 2008; 466:1492-1498.
- Falagas M.E., Roussos N., Gkegkes I.G., Rafailidis P.I., Karageorgopoulos D.E. Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies. Expert Opin Investig Drugs. 2009; 18:921-944.
- Falagas M.E., Kanellopoulou M.D., Karageorgopoulos D.E., Dimopoulos G., Rafailidis P.I., Skarmoutsou N.D. et al. Antimicrobial susceptibility of multidrugresistant Gram negative bacteria to fosfomycin. Eur J Clin Microbiol Infect Dis. 2008; 27:439-443.
- Greish Y.E., Brown P.W. Phase evolution during the formation of stoichiometric hydroxyapatite at 37.4 degrees C. J Biomed Mater Res B Appl Biomater. 2003; 67(1):632- 637.
- Kurkcu M., Benlidayl M.E., Cam B., Sertdemir Y.J. Anorganic bovine-derived hydroxyapatite vs b-tricalcium phosphate in sinus augmentation: a comparative histomorphometric study. Oral Implantol. 2012; (38):519-526.
- Rouse M.S., Piper K.E., Jacobson M., Jacofsky D.J., Steckelberg J.M., Patel R. Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis. J Antimicrob Chemother. 2006; 57(2):301-305.
- Meissner A., Haag R., Rahmanzadeh R. Adjuvant fosfomycin medication in chronic osteomyelitis. Infection. 1989; 17:146-151.
- Thomes B.L., Murray P.K., Bouchier-Hayes D.P. Development of resistant strains of Staphylococcus epidermidis on gentamicin-loaded bone cement in vivo. J Bone Joint Surg. 2002; 84-B:758-760.
- Tunney M.M., Dunne N., Einarson G., McDowel A., Kerr A., Patrick S. Biofilm formation by bacteria isolated from retrieved failed prosthertic hip implants in an in vitro model of hip artroplasty antibiotic prophylaxis. J Orthop Res. 2007; 25(1):2-10.
- Wittmann D.H. Chemotherapeutic principles of difficultto-treat infections in surgery: II. Bone and joint infections. Infection. 1980; 8:330-333.
- Zilberman M., Elsner J.J. Antibiotic-eluting medical devices for various applications. J Controlled Release. 2008; 130:202-215.