Ashby Martin, Petkova Asya, Hilpert Kai
Infection and Immunity Research Institute, St. George's University of London, London, UK *Martin Ashby and Asya Petkova contributed equally.
Curr Opin Infect Dis. 2014 Jun;27(3):258-67. doi: 10.1097/QCO.0000000000000057.
Antimicrobial resistance towards conventional antibiotics is a serious problem for modern medicine and for our society. Multidrug-resistant bacteria are very difficult to treat and treatment options have begun to run out. Here, we summarize the newest studies of drug development using cationic antimicrobial peptides as lead molecules for novel antimicrobial drugs.
A new development is the use of antimicrobial peptides not only as direct antimicrobial lead structures but also using their ability to influence the immune system. Such approaches can be used to develop drugs that influence the immune system in a unique way, supporting specific branches of immune cells in order to clear infection. Applying such an 'immune boost' would also minimize the danger of new resistance emerging in bacteria. In addition, searching for and testing substances that trigger the production of host antimicrobial peptides is still ongoing and opens up a totally new avenue for the use of antimicrobial peptides against infections. Currently, more than 10 clinical trials, phase 2 or 3, using antimicrobial peptides are in progress or have been recently completed.
Multidrug resistance is an urgent problem for modern medicine and novel antimicrobials are needed. Despite some drawbacks, antimicrobial peptides seem now to appear more numerous in clinical trials, indicating the success in developing peptides into novel therapeutics. This can be critical especially for neonates and children, as treatment options for infections with Gram-negatives in neonatal ICUs are becoming rare.
对传统抗生素的耐药性是现代医学和我们社会面临的一个严重问题。多重耐药菌极难治疗,且治疗选择已开始枯竭。在此,我们总结了以阳离子抗菌肽作为新型抗菌药物先导分子的药物研发最新研究。
一个新进展是不仅将抗菌肽用作直接的抗菌先导结构,还利用它们影响免疫系统的能力。此类方法可用于开发以独特方式影响免疫系统的药物,支持免疫细胞的特定分支以清除感染。应用这种“免疫增强”还将使细菌产生新耐药性的风险降至最低。此外,寻找和测试能触发宿主抗菌肽产生的物质的工作仍在进行中,这为利用抗菌肽对抗感染开辟了全新途径。目前,有超过10项使用抗菌肽的2期或3期临床试验正在进行或最近已完成。
多重耐药性是现代医学面临的紧迫问题,需要新型抗菌药物。尽管存在一些缺点,但抗菌肽目前在临床试验中似乎越来越多,这表明将肽开发成新型疗法取得了成功。这对于新生儿和儿童尤为关键,因为新生儿重症监护病房中革兰氏阴性菌感染的治疗选择正变得稀少。