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外用万古霉素治疗大鼠脊柱植入模型中耐甲氧西林表皮葡萄球菌感染

Topical vancomycin for treatment of methicillin-resistant Staphylococcus epidermidis infection in a rat spinal implant model.

作者信息

Karau Melissa J, Zhang Chenghao, Mandrekar Jayawant N, Kohrs Nicholas J, Puleo David A, van Wijnen Andre J, Patel Robin, Boyce Thomas G, Larson A Noelle, Milbrandt Todd A

机构信息

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.

Division of Pediatric Orthopedic Surgery, Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN, 55905, USA.

出版信息

Spine Deform. 2020 Aug;8(4):553-559. doi: 10.1007/s43390-020-00087-4. Epub 2020 Feb 20.

DOI:10.1007/s43390-020-00087-4
PMID:32078142
Abstract

STUDY DESIGN

Basic science.

OBJECTIVE

Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model. Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics.

METHODS

K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed.

RESULTS

Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals' cultures were significantly lower than all other groups (P < 0.0001) with negative culture results, except for one animal. The vancomycin-loaded MS-treated animals had lower bone bacterial counts than the controls (P < 0.0279); blank MS-treated animals had no differences in bacterial densities when compared to non-treated animals.

CONCLUSION

Vancomycin powder and vancomycin-loaded MS were active against MRSE in vitro, in a rat MRSE implant model; however, vancomycin MS were inferior to the topical vancomycin powder. Vancomycin powder prevented MRSE infection in a rat spinal implant infection model.

摘要

研究设计

基础科学。

目的

使用大鼠脊柱模型研究局部应用粉末状万古霉素或悬浮于聚(乳酸-乙醇酸)微球(MS)中的万古霉素治疗感染的能力。手术部位感染(SSIs)是脊柱手术后的一种严重并发症,与高发病率和死亡率相关,且常由凝固酶阴性葡萄球菌引起。已推荐采用综合方法来减少SSIs,包括使用局部万古霉素。动物和人体研究表明,与全身使用抗生素相比,局部使用抗生素对感染的控制效果更佳。

方法

将接种耐甲氧西林表皮葡萄球菌RP62A(MRSE)的克氏针分别用万古霉素粉末、羧甲基纤维素钠盐(CMC)(微球载体)、万古霉素粉末、空白MS或载万古霉素MS在体外处理24或48小时,之后对细菌进行计数。此外,在大鼠中建立脊柱内固定模型,将接种细菌的克氏针植入L4和L5右侧。大鼠不接受治疗或局部用万古霉素粉末、空白MS或载万古霉素MS治疗。8周后,对克氏针、骨骼、软组织和钢丝固定器进行培养并分析结果。

结果

万古霉素粉末和载万古霉素MS在体外残留的细菌明显少于CMC。除一只动物外,万古霉素粉末处理组动物的培养结果显著低于所有其他组(P<0.0001),培养结果为阴性。载万古霉素MS处理组动物的骨骼细菌计数低于对照组(P<0.0279);空白MS处理组动物与未处理动物相比,细菌密度无差异。

结论

在大鼠MRSE植入模型中,万古霉素粉末和载万古霉素MS在体外对MRSE有活性;然而,万古霉素MS不如局部使用的万古霉素粉末。在大鼠脊柱植入感染模型中,万古霉素粉末可预防MRSE感染。

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