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与钴铬合金和聚乙烯相比,预制抗生素骨水泥间隔物可持久防止生物膜形成。

Biofilm Formation is Durably Prevented on Pre-Fabricated Antibiotic Cement Spacers Compared to Cobalt Chrome and Polyethylene.

作者信息

Higashihira Shota, Simpson Stefanie J, Arnold Christopher J, Deckard Evan R, Meneghini R Michael, Greenfield Edward M, Buller Leonard T

机构信息

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana; Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana.

出版信息

J Arthroplasty. 2025 Mar;40(3):779-785. doi: 10.1016/j.arth.2024.08.046. Epub 2024 Sep 2.

Abstract

BACKGROUND

A 2-stage revision remains the standard for managing chronic periprosthetic joint infection. Despite multiple spacer options, whether a particular one better resists biofilm formation remains unclear. Prefabricated polymethylmethacrylate (PMMA) articulating spacers containing antibiotics and a proprietary pore structure were developed to increase antibiotic elution characterized by a rapid burst phase for the initial one to two days and an extended slow-release phase for > 28 days. This in vitro study determined whether biofilm formation is prevented during the initial rapid burst phase and/or the slow-release phase.

METHODS

S. aureus-Xen36 was incubated in 1.5 mL of Luria-Bertani broth with PMMA discs with the proprietary pore structure either with or without gentamycin and vancomycin or with 'Hoffman style' positive-control discs (ultra-high molecular weight polyethylene or cobalt-chrome). Nonadherent bacteria were removed by three phosphate buffered saline rinses every 20 to 24 hours. Planktonic bacterial growth in the culture broth and biofilm formation on the discs were measured by colony forming unit (CFU) counting and resazurin reduction assays. Experiments were repeated > four times.

RESULTS

No detectable planktonic bacterial growth or biofilm formation occurred in cultures containing PMMA with antibiotics (≤ 15 CFUs/disc), whereas biofilms formed on PMMA without antibiotics, ultra-high molecular weight polyethylene, and cobalt-chrome (1 × 10 to 4 × 10 CFUs/disc, P < 0.0001). Biofilm formation was confirmed by a 100-fold decrease in sensitivity to vancomycin. To determine whether the antibiotic slow-release phase is sufficient to block biofilm formation, PMMA discs with antibiotics were preeluted for 14 days with multiple saline changes prior to bacterial inoculation. After antibiotic elution, still no detectable biofilms formed on PMMA discs with antibiotics (≤ 15 CFUs/disc, P < 0.0001).

CONCLUSIONS

Antibiotic release during both the initial and slow-release phases prevented biofilm formation on PMMA with the proprietary pore structure. This may translate into improved infection eradication rates clinically.

摘要

背景

两阶段翻修术仍是治疗慢性人工关节周围感染的标准方法。尽管有多种间隔物可供选择,但尚不清楚哪种间隔物更能有效抵抗生物膜形成。预制的含抗生素和专有孔隙结构的聚甲基丙烯酸甲酯(PMMA)关节间隔物被研发出来,以增加抗生素洗脱,其特点是在最初的一到两天有快速释放期,在超过28天的时间里有延长的缓释期。这项体外研究确定了在最初的快速释放期和/或缓释期是否能防止生物膜形成。

方法

将金黄色葡萄球菌-Xen36接种于1.5 mL含有带专有孔隙结构的PMMA盘的Luria-Bertani肉汤中,PMMA盘分别添加或不添加庆大霉素和万古霉素,或与 “霍夫曼式” 阳性对照盘(超高分子量聚乙烯或钴铬合金)一起培养。每20至24小时用三次磷酸盐缓冲盐水冲洗以去除未黏附的细菌。通过菌落形成单位(CFU)计数和刃天青还原试验来测量培养液中的浮游细菌生长和盘上的生物膜形成。实验重复进行了四次以上。

结果

在含有添加抗生素的PMMA的培养物中未检测到浮游细菌生长或生物膜形成(≤15 CFU/盘),而在未添加抗生素的PMMA、超高分子量聚乙烯和钴铬合金上形成了生物膜(1×10至4×10 CFU/盘,P<0.0001)。对万古霉素敏感性下降100倍证实了生物膜的形成。为了确定抗生素缓释期是否足以阻止生物膜形成,在细菌接种前,对含有抗生素的PMMA盘用多次更换的盐水进行14天的预洗脱。抗生素洗脱后,在含有抗生素的PMMA盘上仍未检测到生物膜形成(≤15 CFU/盘,P<0.0001)。

结论

在初始阶段和缓释阶段的抗生素释放均能防止在具有专有孔隙结构的PMMA上形成生物膜。这在临床上可能转化为提高感染根除率。

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