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在对糖肽类抗生素具有中度耐药性的葡萄球菌所致皮下大鼠盲肠袋移植感染模型中,局部应用天蚕素A和RNAIII抑制肽的预防效果。

Prophylactic efficacy of topical temporin A and RNAIII-inhibiting peptide in a subcutaneous rat Pouch model of graft infection attributable to staphylococci with intermediate resistance to glycopeptides.

作者信息

Cirioni Oscar, Giacometti Andrea, Ghiselli Roberto, Dell'Acqua Giorgio, Gov Yael, Kamysz Wojciech, Lukasiak Jerzy, Mocchegiani Federico, Orlando Fiorenza, D'Amato Giuseppina, Balaban Naomi, Saba Vittorio, Scalise Giorgio

机构信息

Institute of Infectious Diseases and Public Health, University of Ancona, Ancona, Italy.

出版信息

Circulation. 2003 Aug 12;108(6):767-71. doi: 10.1161/01.CIR.0000083717.85060.16. Epub 2003 Jul 28.

Abstract

BACKGROUND

Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by Staphylococcus aureus and Staphylococcus epidermidis with intermediate resistance to glycopeptides.

METHODS AND RESULTS

Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm2 followed by topical inoculation with 2x10(7) colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control group (no graft contamination), a contaminated group that did not receive antibiotic prophylaxis, and 6 contaminated groups that received grafts soaked with temporin A, RIP, rifampin, temporin A plus RIP, RIP plus rifampin, or temporin A plus RIP. The infection was evaluated by quantitative agar culture. When tested alone, temporin A and RIP showed comparable efficacies, and their efficacies were significantly higher than that of rifampin against both strains. All combinations showed efficacies significantly higher than that of each single compound. The combinations of temporin A and RIP exerted the strongest antistaphylococcal efficacies, eliminating infection by 100%.

CONCLUSIONS

The results of the present study make these molecules potentially useful for antimicrobial chemoprophylaxis in vascular surgery.

摘要

背景

附着于植入式医疗设备的细菌在工业和现代医学中发挥着重要作用。葡萄球菌是导致生物材料感染的最常见病原体之一。血管假体移植感染是血管外科医生治疗时最担心出现的并发症之一,常导致住院时间延长、器官衰竭、截肢和死亡。本研究采用大鼠模型,探讨天蚕素A和群体感应抑制剂RNAIII抑制蛋白(RIP)作为预防对糖肽类药物具有中度耐药性的金黄色葡萄球菌和表皮葡萄球菌所致血管假体移植感染的局部疗效。

方法与结果

通过植入1平方厘米的涤纶假体,然后在成年雄性Wistar大鼠背部皮下组织建立移植感染,接着局部接种2×10⁷菌落形成单位的细菌菌株。对于每种葡萄球菌菌株,研究包括一个对照组(无移植污染)、一个未接受抗生素预防的污染组,以及6个接受浸泡有天蚕素A、RIP、利福平、天蚕素A加RIP、RIP加利福平或天蚕素A加RIP的移植组。通过定量琼脂培养评估感染情况。单独测试时,天蚕素A和RIP显示出相当的疗效,且它们对两种菌株的疗效均显著高于利福平。所有组合的疗效均显著高于每种单一化合物。天蚕素A和RIP的组合发挥了最强的抗葡萄球菌疗效,100%消除了感染。

结论

本研究结果表明这些分子在血管外科抗菌化学预防中可能具有潜在用途。

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