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抗菌基因涂层中心静脉导管的体内生物相容性和体外有效性

In vivo biocompatibility and in vitro efficacy of antimicrobial gendine-coated central catheters.

作者信息

Jamal Mohamed A, Hachem Ray Y, Rosenblatt Joel, McArthur Mark J, Felix Edd, Jiang Ying, Tailor Ramesh C, Raad Issam

机构信息

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

出版信息

Antimicrob Agents Chemother. 2015 Sep;59(9):5611-8. doi: 10.1128/AAC.00834-15. Epub 2015 Jun 29.

Abstract

Antimicrobial peripherally inserted central catheters (PICCs) might reduce the incidence of central line-associated bloodstream infections (CLABSI). We tested the biocompatibility of a novel gendine-coated (combination of chlorhexidine [CHX] and gentian violet [GV]) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R)- and CHX-treated PICCs in an in vitro biofilm colonization model. Gendine-coated and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathological analysis was performed at the end of the 4-day period, and circulating levels of CHX and GV in the blood were measured at different time points using liquid chromatography-mass spectrometry. The antimicrobial efficacy of the PICCs was tested following simulated intravascular indwells of 24 h and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida glabrata. Rabbits implanted with gendine-coated PICCs exhibited reduced levels of thrombosis and inflammation compared to those of the rabbits with uncoated controls. No GV was detected in blood samples over the entire study period, and trace concentrations of CHX were detected. The gendine-coated PICCs completely prevented the adherence of all pathogens from 24 h to 1 week (P ≤ 0.001), while M/R-treated, CHX-treated, and control PICCs did not. Gendine-coated PICCs were highly effective in preventing biofilm formation of multidrug-resistant pathogenic bacteria and fungi. Gendine-coated PICCs were biocompatible in an intravascular setting. Further, the pharmacokinetic testing established that acute systemic exposures of CHX and GV from the gendine-coated catheters were well within safe levels.

摘要

抗菌外周静脉穿刺中心静脉导管(PICC)可能会降低中心静脉导管相关血流感染(CLABSI)的发生率。我们在兔血管内模型中测试了一种新型的洁尔碘涂层(洗必泰[CHX]和龙胆紫[GV]的组合)PICC的生物相容性,并在体外生物膜定植模型中与市售的米诺环素/利福平(M/R)和CHX处理的PICC比较测试了抗菌效果。将洁尔碘涂层和未涂层的对照PICC插入兔颈静脉4天。在4天结束时进行组织病理学分析,并使用液相色谱-质谱法在不同时间点测量血液中CHX和GV的循环水平。在模拟血管内留置24小时和1周后,测试PICC对耐甲氧西林金黄色葡萄球菌、耐万古霉素肠球菌、铜绿假单胞菌、大肠杆菌、鲍曼不动杆菌、阴沟肠杆菌、白色念珠菌和光滑念珠菌临床分离株的抗菌效果。与未涂层对照的兔子相比,植入洁尔碘涂层PICC的兔子血栓形成和炎症水平降低。在整个研究期间血液样本中未检测到GV,仅检测到痕量浓度的CHX。洁尔碘涂层PICC在24小时至1周内完全阻止了所有病原体的附着(P≤0.001),而M/R处理、CHX处理和对照PICC则没有。洁尔碘涂层PICC在预防多重耐药病原菌和真菌生物膜形成方面非常有效。洁尔碘涂层PICC在血管内环境中具有生物相容性。此外,药代动力学测试表明,来自洁尔碘涂层导管的CHX和GV的急性全身暴露量完全在安全水平之内。

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