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Drugs. 2018 Aug;78(12):1259-1270. doi: 10.1007/s40265-018-0966-7.
The global threat of the spread of carbapenem resistance in Enterobacteriaceae has led to the search for new antibacterials. Intravenous meropenem/vaborbactam (Vabomere™) is the first carbapenem/β-lactamase inhibitor combination approved in the USA for use in patients with complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a potent inhibitor of class A serine carbapenemases, which, when combined with the antibacterial meropenem, restores the activity of meropenem against β-lactamase producing Enterobacteriaceae, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem/vaborbactam demonstrated excellent in vitro activity against Gram-negative clinical isolates, including KPC- and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. In the phase 3, noninferiority TANGO I trial in patients with cUTIs, intravenous meropenem/vaborbactam was noninferior to intravenous piperacillin/tazobactam for overall success (composite of clinical cure and microbial eradication; FDA primary endpoint) and microbial eradication (EMA primary endpoint). In subsequent superiority testing, meropenem/vaborbactam was superior to piperacillin/tazobactam for overall success. Meropenem/vaborbactam was generally well tolerated, with a tolerability profile generally similar to that of piperacillin/tazobactam. TANGO I did not assess the efficacy of meropenem/vaborbactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and meropenem/vaborbactam is currently not indicated for these patients. Available evidence indicates that meropenem/vaborbactam is a useful treatment option for patients with cUTIs.
肠杆菌科碳青霉烯类耐药的全球威胁促使人们寻找新的抗菌药物。静脉用美罗培南/沃博巴坦(Vabomere™)是首个获得美国批准用于治疗复杂性尿路感染(cUTI),包括肾盂肾炎的碳青霉烯类/β-内酰胺酶抑制剂复合制剂。沃博巴坦是一种强效的 A 类丝氨酸碳青霉烯酶抑制剂,与抗菌药物美罗培南联合使用时,可恢复美罗培南对产β-内酰胺酶的肠杆菌科,尤其是产肺炎克雷伯菌碳青霉烯酶(KPC)的肠杆菌科的活性。美罗培南/沃博巴坦对包括产 KPC 和产超广谱β-内酰胺酶(ESBL)的肠杆菌科在内的革兰氏阴性临床分离株具有良好的体外活性。在 3 期非劣效性 TANGO I 临床试验中,治疗 cUTI 的患者中,静脉用美罗培南/沃博巴坦与静脉用哌拉西林/他唑巴坦相比,整体疗效(临床治愈率和微生物清除率的复合终点;FDA 主要终点)和微生物清除率(EMA 主要终点)均不劣效。在随后的优效性检验中,美罗培南/沃博巴坦在整体疗效方面优于哌拉西林/他唑巴坦。美罗培南/沃博巴坦总体耐受性良好,其耐受性与哌拉西林/他唑巴坦相似。TANGO I 并未评估美罗培南/沃博巴坦治疗耐碳青霉烯类肠杆菌科感染的疗效,目前该药不适用于这些患者。现有证据表明,美罗培南/沃博巴坦是治疗 cUTI 患者的一种有效治疗选择。