a College of Pharmacy , University of Illinois at Chicago , Chicago , IL , USA.
b College of Medicine , University of Illinois at Chicago , Chicago , IL , USA.
Expert Opin Drug Metab Toxicol. 2018 Oct;14(10):1007-1021. doi: 10.1080/17425255.2018.1511702. Epub 2018 Sep 19.
Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.
美罗培南/沃博巴坦(M/V)是首个获批用于治疗复杂性尿路感染(cUTI),包括肾盂肾炎的碳青霉烯类和β-内酰胺酶抑制剂合剂。沃博巴坦是一种新型硼酸β-内酰胺酶抑制剂,对包括肺炎克雷伯菌碳青霉烯酶(KPC)在内的丝氨酸β-内酰胺酶具有高亲和力。这种合剂,Vabomere™,于 2017 年 8 月被美国食品和药物管理局批准用于治疗 18 岁及以上患者的 cUTI,包括由以下敏感微生物引起的肾盂肾炎:大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌属复合菌。涵盖领域:将讨论有关微生物学、药代动力学、药效学以及评估疗效、安全性和耐受性的临床试验的相关文献。专家意见:对于产 KPC 感染,如氨基糖苷类、多黏菌素、磷霉素和替加环素等治疗选择存在疗效、毒性、最佳剂量和/或耐药性方面的担忧。此外,对头孢他啶/阿维巴坦新合剂的耐药性也已经出现。目前支持使用 M/V 治疗产 KPC 感染的临床证据仅限于一项针对少数严重感染患者的开放标签、随机、III 期研究,这些患者感染的是耐碳青霉烯类肠杆菌科细菌。尽管 M/V 未批准用于产 KPC 感染,但我们认为 M/V 将成为产 KPC 肠杆菌科感染的首选药物。