a Center for Anti-Infective Research and Development , Hartford Hospital , Hartford , CT , USA.
Expert Opin Investig Drugs. 2018 Apr;27(4):325-338. doi: 10.1080/13543784.2018.1460354. Epub 2018 Apr 10.
Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) are associated with significant mortality and costs. New drugs in development to combat these difficult-to-treat infections primarily target carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumannii.
The authors summarize in vitro and in vivo efficacy studies, as well as available clinical trial findings, for new agents in development for treatment of infection caused by MDR-GNB. Information regarding dosage regimens utilized in clinical trials and key pharmacokinetic and pharmacodynamic considerations are provided if available. A summary of recently approved agents, delafloxacin and meropenem/vaborbactam, is also included.
The development of multiple novel agents to fight MDR-GNB is promising to help save the lives of patients who acquire infection, and judicious use of these agents is imperative once they come to market to prevent the development of resistance. The other component paramount to this field of research is implementation of effective infection control policies and carbapenem-resistant Enterobacteriaceae (CRE) carrier screening protocols to mitigate the worldwide spread of MDR-GNB. Further investigation of anti-infective synergistic combinations will also be important, as well as support for economic research to reveal the true cost-benefit of utilization of the new agents discussed herein.
由耐多药革兰氏阴性菌（MDR-GNB）引起的感染与显著的死亡率和成本相关。为了应对这些难以治疗的感染，新开发的药物主要针对耐碳青霉烯类肠杆菌科、耐多药铜绿假单胞菌和耐多药鲍曼不动杆菌。
作者总结了新开发药物治疗耐多药革兰氏阴性菌感染的体外和体内疗效研究以及可用的临床试验结果。如果有可用的信息，将提供临床试验中使用的剂量方案以及关键的药代动力学和药效学考虑因素。最近批准的药物，德拉沙星和美罗培南/比阿培南，的概要也包括在内。
开发多种新型药物来对抗 MDR-GNB 有望帮助挽救感染患者的生命，一旦这些药物上市，明智地使用这些药物对于防止耐药性的发展至关重要。该研究领域的另一个至关重要的因素是实施有效的感染控制政策和耐碳青霉烯类肠杆菌科（CRE）携带者筛查方案，以减轻 MDR-GNB 在全球的传播。进一步研究抗感染协同组合也很重要，同时还需要支持经济研究，以揭示本文讨论的新药物的实际成本效益。
