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负载利福平、克拉霉素、多西环素单独或联合使用的甲基丙烯酸酯基共聚物薄膜对生物膜形成的预防作用

Prevention of biofilm formation by methacrylate-based copolymer films loaded with rifampin, clarithromycin, doxycycline alone or in combination.

作者信息

Rose Warren E, Otto Daniel P, Aucamp Marique E, Miller Zach, de Villiers Melgardt M

机构信息

School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin, 53705-2222, USA.

出版信息

Pharm Res. 2015 Jan;32(1):61-73. doi: 10.1007/s11095-014-1444-x. Epub 2014 Jun 17.

Abstract

PURPOSE

This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention.

BACKGROUND

Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management.

METHODS

The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated.

RESULTS

In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided >99.9% kill of an MRSA inoculate for up to 72 h.

CONCLUSION

Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.

摘要

目的

本研究报告了利福平、强力霉素和克拉霉素这三种抗生素掺入聚(苯乙烯-共-甲基丙烯酸甲酯)薄膜及其对生物膜预防的影响。

背景

患者进行侵入性操作,如手术器械、静脉或导尿管植入,往往会导致复杂的医院获得性医院感染。生物膜形成对于在这些器械上引发这些感染至关重要,因此需要新的抗生素递送方法来进行更有效的管理。

方法

对薄膜进行体外药物释放评估,以及评估其对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌生物膜形成的预防能力。还研究了通过接触角测量获得的表面张力成分,以及通过扫描电子显微镜评估的薄膜形态。

结果

在本研究中,载有抗生素的甲基丙烯酸共聚物薄膜在体外生物反应器模型中进行测试时,能有效释放利福平、克拉霉素和强力霉素长达21天,可预防生物膜形成。这些载药共聚物薄膜具有优势,即一旦抗生素从聚合物表面溶解,其涂层材料具有一种新表面,不适合生物膜重新附着。从聚合物薄膜释放的利福平和克拉霉素组合在长达72小时内对耐甲氧西林金黄色葡萄球菌接种物的杀灭率>99.9%。

结论

结果表明,将多种药物与具有独特表面性质、初始亲水性和粗糙度增加的共聚物薄膜相结合,可能是预防生物膜形成的有效方法。

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