University of Queensland Centre for Clinical Research.
Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Curr Opin Infect Dis. 2020 Apr;33(2):214-223. doi: 10.1097/QCO.0000000000000627.
Multidrug-resistant (MDR) Gram-negative bacteria infections are listed among the top public health threats of the current era. As a result, there has been an increase in efforts to develop new therapeutic agents against MDR Gram-negatives. The purpose of this review is to summarize the clinical and preclinical findings associated with recently approved drugs and the drugs in clinical development against ESBL and carbapenemase-producing Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii infections.
There are a number of ESBL active agents in late stage clinical development that can help spare carbapenems. Likewise, recently approved β-lactam/β-lactamase inhibitor combinations allow a change in the treatment of KPC and OXA-48 producers and carbapenem-resistant P. aeruginosa from colistin to new, safer agents. Treatment of Meta-beta-lactamase (MBL) producers remains an unmet need - apart from cefiderocol, most agents with MBL activity are still in clinical development. Among the few agents with carbapenem-resistant A. baumannii activity, durlobactam/sulbactam in phase III clinical trials provides hope.
Armamentarium against MDR Gram-negatives has expanded with the dominance of agents active against ESBL and KPC producers. There is a need to prioritize MBL producers and carbapenem-resistant A. baumannii, as well as the need for clinical trials to test the new agents against serious infections.
耐多药(MDR)革兰氏阴性菌感染被列为当前时代的主要公共卫生威胁之一。因此,人们加大了开发针对 MDR 革兰氏阴性菌的新治疗药物的力度。本综述的目的是总结最近批准的药物以及针对产 ESBL 和碳青霉烯酶肠杆菌科、耐碳青霉烯铜绿假单胞菌和耐碳青霉烯鲍曼不动杆菌感染的临床和临床前研究结果。
有许多处于后期临床开发阶段的 ESBL 活性药物可以帮助节省碳青霉烯类药物。同样,最近批准的β-内酰胺/β-内酰胺酶抑制剂联合用药使 KPC 和 OXA-48 产生者以及耐碳青霉烯类铜绿假单胞菌的治疗方法从粘菌素改为新的、更安全的药物。治疗金属β-内酰胺酶(MBL)产生者仍然是一个未满足的需求-除头孢他啶外,大多数具有 MBL 活性的药物仍处于临床开发阶段。在少数具有耐碳青霉烯类鲍曼不动杆菌活性的药物中,durlobactam/sulbactam 处于 III 期临床试验阶段,带来了希望。
针对 MDR 革兰氏阴性菌的药物已经扩大,具有针对 ESBL 和 KPC 产生者的活性的药物占据主导地位。需要优先考虑 MBL 产生者和耐碳青霉烯类鲍曼不动杆菌,同时需要临床试验来测试新药物对严重感染的疗效。