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抗菌肽人乳铁蛋白1-11与庆大霉素在慢性耐甲氧西林金黄色葡萄球菌骨髓炎模型中的疗效比较

Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model.

作者信息

Faber Christopher, Stallmann Hein P, Lyaruu D M, Joosten Uwe, von Eiff Christof, van Nieuw Amerongen Arie, Wuisman Paul I J M

机构信息

Department of Orthopaedic Surgery, VU University Medical Center, P. O. Box 7057, 1007 MB Amsterdam, The Netherlands.

出版信息

Antimicrob Agents Chemother. 2005 Jun;49(6):2438-44. doi: 10.1128/AAC.49.6.2438-2444.2005.

Abstract

The therapeutic efficacy of an antimicrobial peptide, human lactoferrin 1-11 (hLF1-11), was investigated in a model of chronic methicillin-resistant Staphylococcus aureus (MRSA) (gentamicin susceptible) osteomyelitis in rabbits. We incorporated 50 mg hLF1-11/g or 50 mg gentamicin/g cement powder into a calcium phosphate bone cement (Ca-P) and injected it into the debrided tibial cavity, creating a local drug delivery system. The efficacy of hLF1-11 and gentamicin was compared to that of a sham-treated control (plain bone cement) (n=6) and no treatment (infected only) (n=5). The results were evaluated by microbiology, radiology, and histology. MRSA was recovered from all tibias in both control groups (n=11). On the other hand, hLF1-11 and gentamicin significantly reduced the bacterial load. Furthermore, no growth of bacteria was detected in five out of eight and six out of eight specimens of the hLF1-11- and gentamicin-treated groups, respectively. These results were confirmed by a significant reduction of the histological disease severity score by hLF1-11 and gentamicin compared to both control groups. The hLF1-11-treated group also had a significantly lower radiological score compared to the gentamicin-treated group. This study demonstrates the efficacy of hLF1-11 incorporated into Ca-P bone cement as a possible therapeutic strategy for the treatment of osteomyelitis, showing efficacy comparable to that of gentamicin. Therefore, the results of this study warrant further preclinical investigations into the possibilities of using hLF1-11 for the treatment of osteomyelitis.

摘要

在兔慢性耐甲氧西林金黄色葡萄球菌(MRSA)(对庆大霉素敏感)骨髓炎模型中,研究了抗菌肽人乳铁蛋白1-11(hLF1-11)的治疗效果。我们将50 mg hLF1-11/g或50 mg庆大霉素/g的水泥粉末掺入磷酸钙骨水泥(Ca-P)中,并将其注入清创后的胫骨腔,创建了一个局部药物递送系统。将hLF1-11和庆大霉素的疗效与假手术对照组(普通骨水泥)(n = 6)和未治疗组(仅感染)(n = 5)进行比较。通过微生物学、放射学和组织学评估结果。在两个对照组(n = 11)的所有胫骨中均检出MRSA。另一方面,hLF1-11和庆大霉素显著降低了细菌载量。此外,hLF1-11治疗组和庆大霉素治疗组分别有八分之五和八分之六的标本未检测到细菌生长。与两个对照组相比,hLF1-11和庆大霉素显著降低了组织学疾病严重程度评分,证实了这些结果。与庆大霉素治疗组相比,hLF1-11治疗组的放射学评分也显著更低。本研究证明了掺入Ca-P骨水泥中的hLF1-11作为治疗骨髓炎的一种可能治疗策略的疗效,显示出与庆大霉素相当的疗效。因此,本研究结果值得进一步进行临床前研究,以探讨使用hLF1-11治疗骨髓炎的可能性。

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