a Alfa Institute of Biomedical Sciences , Athens , Greece.
b Laboratory of Pharmacokinetics and Toxicology , Department of Pharmacy, 401 General Military Hospital , Athens , Greece.
Expert Rev Anti Infect Ther. 2019 Jun;17(6):387-401. doi: 10.1080/14787210.2019.1610392. Epub 2019 May 27.
: The constantly increasing spread of severe infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) is a critical threat to the global medical community. After a long period of antibiotic pipeline pause, new antibiotic compounds are commercially available or are at late stages of clinical evaluation, promising to augment the therapeutic armamentarium of clinicians against deadly pathogens. : This review summarizes available data regarding agents with potent activity against critical MDR Gram-negative pathogens, which urgently require new efficient antibiotics. Recently approved antibiotic formulations; and agents in advanced stages of development, including combinations of β-lactam/β-lactamase inhibitor, novel cephalosporins (cefiderocol), tetracyclines (eravacycline), aminoglycosides (plazomicin), quinolones (delafloxacin and finafloxacin) and pleuromutilins (lefamulin) are discussed in this review. : The recent introduction of new antibiotics into clinical practice is an encouraging step after a long period of pipeline stagnation. New formulations will be a useful option for clinicians to treat serious infections caused by several MDR Gram-negative pathogens. However, most of the new compounds are based on modifications of traditional antibiotic structures challenging their longevity as therapeutic options. More investment is needed for the discovery and clinical development of truly innovative and effective antibiotics without cross-resistance to currently used antibiotics.
: 由于耐多药(MDR)革兰氏阴性菌(GNB)引起的严重感染不断蔓延,对全球医学界构成了严重威胁。在抗生素研发管道长期停滞之后,新的抗生素化合物已经上市或处于临床评估后期,有望为临床医生对抗致命病原体的治疗手段增添新武器。 : 本文综述了针对急需新型高效抗生素的关键 MDR 革兰氏阴性病原体具有强大活性的现有药物的数据。本文讨论了最近批准的抗生素制剂,以及处于研发后期的药物,包括β-内酰胺/β-内酰胺酶抑制剂联合制剂、新型头孢菌素(头孢地尔)、四环素(依拉环素)、氨基糖苷类(普拉佐米星)、喹诺酮类(德拉沙星和芬氟拉明)和截短侧耳素(利福米特)。 : 在抗生素研发管道长期停滞之后,最近将新抗生素引入临床实践是一个令人鼓舞的举措。新制剂将为临床医生治疗由几种 MDR 革兰氏阴性病原体引起的严重感染提供一个有用的选择。然而,大多数新化合物都是基于传统抗生素结构的修饰,这对它们作为治疗选择的持久性构成了挑战。需要更多的投资来发现和开发真正创新和有效的抗生素,而这些抗生素不应与目前使用的抗生素产生交叉耐药性。