Infectious Diseases Unit, Policlinico San Martino Hospital - IRCCS.
Department of Health Sciences (DISSAL), University of Genoa, Genoa.
Curr Opin Infect Dis. 2023 Dec 1;36(6):615-622. doi: 10.1097/QCO.0000000000000984. Epub 2023 Oct 16.
Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB.
Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii . Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti- Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound.
Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.
由于可供选择的治疗方法有限,且这些方法常常存在毒性和不良药代动力学特征等问题,因此,非发酵革兰氏阴性菌(NF-GNB)引起的严重感染对临床医生构成了重大挑战。本文旨在简要概述目前针对 NF-GNB 的抗感染药物研发的相关数据。
目前有几种针对 NF-GNB 具有疗效的药物正在进行临床试验。多利培南-舒巴坦和头孢吡肟-他唑巴坦有望成为治疗耐碳青霉烯鲍曼不动杆菌的新方法。头孢吡肟-阿维巴坦可能是治疗由多种 NF-GNB 引起的尿路感染的合适选择。头孢吡肟-恩美曲巴坦对多种 NF-GNB 菌株具有强大的体外活性,但现有数据不足以证明其作为抗假单胞菌药物的作用。西罗莫司他是一种广泛的β-内酰胺酶抑制剂,可与多种药物联合使用,增强这些药物对许多 NF-GNB 的体外活性,包括对新型、更广泛谱的药物耐药的菌株。最后,美罗培南对严重的铜绿假单胞菌感染似乎是一种有前途的针对病原体的解决方案;但需要进一步研究以确定该化合物的安全性。
本文综述的每种新型分子均对 NF-GNB 具有有趣的体外活性范围。此外,其中一些已在体内证明有效,这突出了它们作为未来治疗选择的潜力。