Lynch Susan V, Wiener-Kronish Jeanine P
Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California 94143, USA.
Curr Opin Crit Care. 2008 Oct;14(5):593-9. doi: 10.1097/MCC.0b013e32830f1dd5.
Incidences of antimicrobial-resistant infections have increased dramatically over the past several decades and are associated with adverse patient outcomes. Alternative approaches to combat infection are critical and have led to the development of more specific drugs targeted at particular bacterial virulence systems or essential regulatory pathways. The purpose of this review is to highlight the recent developments in antibacterial therapy and the novel approaches toward increasing our therapeutic armory against bacterial infection.
Although classic antibiotic development is not occurring rapidly, alternative therapeutics that target specific bacterial virulence systems are progressing from the discovery stage through the Food and Drug Administration approval process. Here we review novel antibodies that target specific virulence systems as well as a variety of newly discovered small molecules that block bacterial attachment, communication systems (quorum sensing) or important regulatory processes associated with virulence gene expression.
The success of novel therapeutics could significantly change clinical practice. Furthermore, the complications of collateral damage due to antibiotic administration, for example, suprainfections or decreased host immunity due to loss of synergistic bacterial communities, may be minimized using therapeutics that specifically target pathogenic behavior.
在过去几十年中,抗菌药物耐药性感染的发生率急剧上升,且与不良患者预后相关。对抗感染的替代方法至关重要,并促使人们开发出更具针对性的药物,这些药物靶向特定的细菌毒力系统或关键调控途径。本综述的目的是强调抗菌治疗的最新进展以及增加我们对抗细菌感染治疗手段的新方法。
尽管经典抗生素的研发进展并不迅速,但靶向特定细菌毒力系统的替代疗法正从发现阶段进入美国食品药品监督管理局的审批流程。在此,我们综述了靶向特定毒力系统的新型抗体以及多种新发现的小分子,这些小分子可阻断细菌黏附、通讯系统(群体感应)或与毒力基因表达相关的重要调控过程。
新型疗法的成功可能会显著改变临床实践。此外,使用专门针对致病行为的疗法,可将抗生素给药所致附带损害的并发症(例如,重叠感染或由于协同细菌群落丧失导致的宿主免疫力下降)降至最低。