RNAIII-inhibiting peptide significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of central venous catheter -: Associated Staphylococcus aureus infections

RNAIII-inhibiting peptide significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of central venous catheter -: Associated Staphylococcus aureus infections
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DOI:
10.1086/498914
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发表时间:
2006-01-15
影响因子:
6.4
通讯作者:
Balaban, N
Balaban, N
中科院分区:
医学2区
文献类型:
--
作者:
Cirioni, O;Giacometti, A;Balaban, N

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背景。临床实践中使用的医疗器械常常与生物膜相关的葡萄球菌感染有关。方法。使用 96 孔聚苯乙烯组织培养板对金黄色葡萄球菌生物膜进行体外抗生素敏感性测定,以测试 RNAIII 抑制肽 (RIP)、环丙沙星、亚胺培南和万古霉素的作用。使用中心静脉导管(CVC)相关感染的大鼠模型进行功效研究。植入后二十四小时,导管充满 RIP (1 mg/mL)。三十分钟后,通过 CVC,用金黄色葡萄球菌史密斯扩散菌株的 cfu 攻击大鼠。 24小时后开始抗生素锁1.0 x 10(6)技术。结果。生物膜中抗生素的最低抑制浓度比对自由生长的浮游细胞的最低抑制浓度高至少 4 倍。当它们第一次接受 RIP 处理时,生物膜中的细胞与浮游细胞一样对抗生素敏感。这些数据得到了体内研究的证实。特别是,当CVC同时用RIP和抗生素处理时,生物膜细菌负荷进一步降低至1 x 10(1) cfu/mL,并且未检测到菌血症,表明菌血症100%消除,生物膜细菌负荷减少6 log(10)。结论。 RIP 可显着降低细菌负荷并增强抗生素治疗 CVC 相关金黄色葡萄球菌感染的效果。
Background. Medical devices used in clinical practice are often associated with biofilm-associated staphylococcal infections.Methods. An in vitro antibiotic susceptibility assay of Staphylococcus aureus biofilms using 96-well polystyrene tissue-culture plates was performed to test the effects of RNAIII-inhibiting peptide ( RIP), ciprofloxacin, imipenem, and vancomycin. Efficacy studies were performed using a rat model of central venous catheter (CVC)-associated infection. Twenty-four hours after implantation, the catheters were filled with RIP (1 mg/mL). Thirty minutes later, rats were challenged, via the CVC, with cfu of S. aureus strain Smith diffuse. The antibiotic-lock 1.0 x 10(6) technique was begun 24 h later.Results. Minimum inhibitory concentrations of antibiotics in biofilms were at least 4-fold higher than those against the freely growing planktonic cells. When they were first treated with RIP, the cells in biofilms became as susceptible to antibiotics as did planktonic cells. These data were confirmed by the in vivo studies. In particular, when CVCs were treated with both RIP and antibiotics, the biofilm bacterial load was further reduced to 1 x 10(1) cfu/mL, and bacteremia was not detected, suggesting that there was 100% elimination of bacteremia and a 6 log(10) reduction in biofilm bacterial load.Conclusion. RIP significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of CVC-associated S. aureus infections.