Smith Anthony W
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
Adv Drug Deliv Rev. 2005 Jul 29;57(10):1539-50. doi: 10.1016/j.addr.2005.04.007.
The conventional view of antibiotic resistance is one where bacteria exhibit significantly reduced susceptibility to antimicrobials in laboratory tests by mechanisms such as altered drug uptake, altered drug target and drug inactivation. Whilst these mechanisms undoubtedly make a major contribution to antibiotic failure in the clinic, the phenomenon of clinical failure in spite of sensitivity in laboratory tests is also well recognised. It is in this context that attention has focussed on bacteria growing as adherent biofilms, not only as the mode of growth of device-related infections associated for example with artificial joints and venous catheters, but also with other chronic infections such as those occurring in the respiratory tract. Growth as a biofilm almost always leads to a significant decrease in susceptibility to antimicrobial agents compared with cultures grown in suspension and, whilst there is no generally agreed mechanism for the resistance of biofilm bacteria, it is largely phenotypic. That is, when biofilm bacteria are grown in conventional laboratory suspension culture they become susceptible to antimicrobials. A number of elements in the process of biofilm formation have been studied as targets for novel drug delivery technologies. These include surface modification of devices to reduce bacterial attachment and biofilm development as well as incorporation of antimicrobials-again to prevent colonisation. Electrical approaches have been used either to release antimicrobials from device surfaces or to drive antimicrobials through the biofilm. Other technologies not specifically focussed on biofilms include aerosolized delivery of antibiotics to the lung and formulation into liposome and polymer-based vehicles. Liposomal systems have been widely studied, either to target antibiotics to the surface of bacterial biofilms, or by virtue of their property of being taken up cells of the reticuloendothelial system, to target antibiotics towards intracellular bacteria. Many polymer-based carrier systems have also been proposed, including those based on biodegradable polymers such as poly(lactide-co-glycolide) as well as thermoreversible hydrogels. Their contribution to the prevention or resolution of infection is reviewed.
对抗生素耐药性的传统观点认为，在实验室测试中，细菌通过改变药物摄取、改变药物靶点和药物失活等机制，对抗微生物药物的敏感性显著降低。虽然这些机制无疑是导致临床抗生素治疗失败的主要原因，但尽管在实验室测试中显示敏感，临床上仍出现治疗失败的现象也广为人知。正是在这种背景下，人们将注意力集中在以附着生物膜形式生长的细菌上，这不仅是与人工关节和静脉导管等相关的器械相关感染的生长模式，也是其他慢性感染（如呼吸道感染）的生长模式。与悬浮培养的细菌相比，以生物膜形式生长几乎总是导致对抗菌剂的敏感性显著降低，虽然对于生物膜细菌耐药性尚无普遍认可的机制，但很大程度上是表型耐药。也就是说，当生物膜细菌在传统实验室悬浮培养中生长时，它们会变得对抗菌药物敏感。生物膜形成过程中的一些因素已作为新型药物递送技术的靶点进行了研究。这些因素包括对器械进行表面改性以减少细菌附着和生物膜形成，以及加入抗菌剂——同样是为了防止细菌定植。已采用电学方法从器械表面释放抗菌剂或促使抗菌剂穿透生物膜。其他并非专门针对生物膜的技术包括将抗生素雾化递送至肺部以及制成脂质体和聚合物载体。脂质体系统已得到广泛研究，要么将抗生素靶向细菌生物膜表面，要么凭借其被网状内皮系统细胞摄取的特性，将抗生素靶向细胞内细菌。还提出了许多基于聚合物的载体系统，包括基于聚（丙交酯 - 乙交酯）等可生物降解聚合物以及热可逆水凝胶的载体系统。本文综述了它们在预防或解决感染方面的作用。
