Abstract

Objective Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA).

Materials and Methods Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed.

Results Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats.

Clinical Significance The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics.

Authors' Contributions

Hamid Staji and Maryam Rassouli generated hypothesis, experimental design, real-time polymerase chain reaction experiment and LS extraction. Bahareh Gerivani, Nooshin Ghazaleh and Abbas Javaheri Vayeghan conducted the experiments including surgery, pathology and enzyme-linked immunosorbent assay. Hamid Staji and Maryam Rassouli interpreted and analysed the results and wrote the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for author contributions for this manuscript, take responsibility for the integrity of the work as a whole and have given final approval to the version to be published.

中文翻译：

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红霉素和水ch唾液提取物的共同给药可减轻耐甲氧西林金黄色葡萄球菌诱导的大鼠骨髓炎。

摘要

目的在体外条件下， 红霉素（Ery）和水ech（LS）可以抑制金黄色葡萄球菌的生长。这项研究旨在评估Ery和LS在耐甲氧西林金黄色葡萄球菌（MRSA）诱导的雄性Wistar大鼠胫骨慢性骨髓炎中的活性和协同作用。

材料和方法 诱导骨髓炎的四周后，将大鼠分为四组，包括不治疗（对照组），Ery单药（口服），LS单药或Ery + LS每天两次，共2周。评估了金黄色葡萄球菌的生长，病理征象和炎性细胞因子肿瘤坏死因子-α（TNF-α）的水平。

结果 大鼠在实验过程中很好地耐受了所有治疗策略。单独进行Ery治疗可显着降低细菌生长，病理征象和TNF-α水平。单独的水significantly唾液可以显着降低TNF-α的水平，但并不能使细菌的生长和病理征兆显着降低。与其他组相比，Ery + LS治疗显着降低了细菌生长，显着减轻了骨病理征象并降低了TNF-α水平。统计分析表明，Ery和LS在对抗MRSA诱导的大鼠骨髓炎时具有更强的功效和协同作用。

临床意义 本研究表明，当与Ery或其他疗法联合使用时，LS可能具有治疗MRSA诱导的骨髓炎的临床效用。

作者的贡献

Hamid Staji和Maryam Rassouli提出了假设，实验设计，实时聚合酶链反应实验和LS提取。Bahareh Gerivani，Nooshin Ghazaleh和Abbas Javaheri Vayeghan进行了包括外科手术，病理学和酶联免疫吸附测定在内的实验。Hamid Staji和Maryam Rassouli解释并分析了结果并撰写了手稿。所有具名作者均符合国际医学杂志编辑委员会（ICMJE）对该稿件的贡献标准，对整个作品的完整性负责，并最终批准了即将出版的版本。