Efficacy of lysostaphin-coated titanium plates on implant-associated MRSA osteitis in minipigs,European Journal of Trauma and Emergency Surgery

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Efficacy of lysostaphin-coated titanium plates on implant-associated MRSA osteitis in minipigs
European Journal of Trauma and Emergency Surgery ( IF 1.9 ) Pub Date : 2024-01-24 , DOI: 10.1007/s00068-024-02448-4
Carina Jaekel ₁ , Ceylan D Windolf ₁ , Dan Bieler _{1,

2} , Lisa Oezel ₁ , Lars F Seiler ₁ , Felix N Lakomek ₁ , Christoph Beyersdorf ₁ , Jann Mertens ₃ , Andrea Steuwe ₄ , Joachim Windolf ₁ , Jan P Grassmann ₅

Affiliation

Purpose

The growing incidence of implant-associated infections (IAIs) caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance to antibiotics requires new therapeutic strategies. Lysostaphin has been shown to eliminate this biofilm. Own studies confirm the effectiveness in a murine model. The current study characterizes the effects of lysostaphin-coated plates in an IAI minipig model.

Methods

The femur of 30 minipigs was stabilized with a five-hole plate, a bone defect was created, and in 20 cases methicillin-resistant Staphylococcus aureus was applied. Ten animals served as control group. After 14 days, local debridement, lavage, and plate exchange (seven-hole plate) were performed. Ten of the infected minipigs received an uncoated plate and 10 a lysostaphin-coated plate. On day 84, the minipigs were again lavaged, followed by euthanasia. Bacterial load was quantified by colony-forming units (CFU). Immunological response was determined by neutrophils, as well as interleukins. Fracture healing was assessed radiologically.

Results

CFU showed significant difference between infected minipigs with an uncoated plate and minipigs with a lysostaphin-coated plate (p = 0.0411). The infection-related excessive callus formation and calcification was significantly greater in the infected animals with an uncoated plate than in animals with a lysostaphin-coated plate (p = 0.0164/p = 0.0033). The analysis of polymorphonuclear neutrophils and interleukins did not reveal any pioneering findings.

Conclusion

This study confirms the minipig model for examining IAI. Furthermore, coating of plates using lysostaphin could be a promising tool in the therapeutic strategies of IAI. Future studies should focus on coating technology of implants and on translation into a clinical model.

中文翻译：

溶葡萄球菌素涂层钛板对小型猪种植体相关 MRSA 骨炎的疗效

目的

由形成生物膜的金黄色葡萄球菌引起的种植体相关感染 (IAI) 的发病率不断上升，加上抗生素耐药性不断增加，需要新的治疗策略。溶葡萄球菌素已被证明可以消除这种生物膜。自己的研究证实了小鼠模型的有效性。目前的研究描述了溶葡萄球菌素包被的平板在 IAI 小型猪模型中的作用。

方法

用五孔板固定30只小型猪的股骨，制造骨缺损，并在20例中应用耐甲氧西林金黄色葡萄球菌。十只动物作为对照组。 14天后，进行局部清创、灌洗、换板（七孔板）。 10 只受感染的小型猪接受未包被的平板，10 只接受溶葡萄球菌素包被的平板。第 84 天，再次对小型猪进行灌洗，然后实施安乐死。细菌负荷通过菌落形成单位（CFU）进行量化。免疫反应由中性粒细胞和白细胞介素决定。通过放射学评估骨折愈合情况。

结果

使用未包被的平板的受感染小型猪和使用溶葡萄球菌素包被的平板的小型猪之间的 CFU 显示出显着差异（ p = 0.0411）。在使用未包被的平板的受感染动物中，与感染相关的过度愈伤组织形成和钙化明显大于使用溶葡萄球菌素包被的平板的动物（ p = 0.0164/ p = 0.0033）。对多形核中性粒细胞和白细胞介素的分析没有揭示任何开创性的发现。