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从再生骨移植替代物中洗脱的庆大霉素的药代动力学:体外和临床释放研究。

Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies.

作者信息

Stravinskas M, Horstmann P, Ferguson J, Hettwer W, Nilsson M, Tarasevicius S, Petersen M M, McNally M A, Lidgren L

机构信息

Orthopaedic Surgeon, Lithuanian University of Health, Eivenių str. 2, LT-50009 Kaunas, Lithuania.

Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.

出版信息

Bone Joint Res. 2016 Sep;5(9):427-35. doi: 10.1302/2046-3758.59.BJR-2016-0108.R1.

DOI:10.1302/2046-3758.59.BJR-2016-0108.R1
PMID:27678329
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5047051/
Abstract

OBJECTIVES

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

MATERIALS AND METHODS

We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.

RESULTS

The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years).

CONCLUSIONS

This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials.Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427-435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1.

摘要

目的

深部骨与关节感染(DBJI)与健康、人口老龄化以及幸福安康直接相关。老年人群更容易感染,而疼痛、生活质量下降、发病率、旷工以及因残疾导致的提前退休等后果给本就不堪重负的医疗系统和社会预算带来了巨大负担。由于坏死骨血管灌注不良、大的骨缺损以及基于生物膜的持续性感染,DBJI对全身用抗生素的反应较差。新出现的细菌耐药性构成了重大威胁,迫切需要新的创新治疗方法来遏制其当前的发展态势。

材料与方法

我们展示了一种由羟基磷灰石和硫酸钙组成的新型双相陶瓷骨替代物,用于局部抗生素递送并促进骨再生。在四种情况下测量庆大霉素的释放:1)在林格氏溶液中进行体外洗脱;2)在接受转子间髋部骨折治疗或非骨水泥型髋关节翻修的患者中进行局部洗脱;3)在接受骨肿瘤切除术的患者中进行局部洗脱;4)在接受慢性皮质骨髓炎手术治疗的患者中进行局部洗脱。

结果

体外释放模式与患者研究中获得的释放情况相当。在最新随访(至少1.5年)时,骨髓炎组未检测到复发。

结论

这种含抗生素的新型双相骨替代物可在一系列临床情况下安全预防骨感染。体外测试方法可预测体内性能,使其成为未来抗生素洗脱骨再生材料开发中的可靠工具。引用本文:M. 斯特拉温斯卡、P. 霍斯特曼、J. 弗格森、W. 赫特韦尔、M. 尼尔森、S. 塔拉塞维丘斯、M. M. 彼得森、M. A. 麦克纳利、L. 利德格伦。从再生骨移植替代物中洗脱的庆大霉素的药代动力学:体外和临床释放研究。《骨关节研究》2016;5:427 - 435。DOI:10.1302/2046 - 3758.59.BJR - 2016 - 0108.R1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/b1bb3f8aae0b/bonejointres-05-427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/53cb65aa15ac/bonejointres-05-427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/44ca3f005da0/bonejointres-05-427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/d8c0ce0269bf/bonejointres-05-427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/938c6e167ea2/bonejointres-05-427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/b1bb3f8aae0b/bonejointres-05-427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/53cb65aa15ac/bonejointres-05-427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/44ca3f005da0/bonejointres-05-427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/d8c0ce0269bf/bonejointres-05-427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/938c6e167ea2/bonejointres-05-427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540f/5047051/b1bb3f8aae0b/bonejointres-05-427-g005.jpg

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