Imipenem-Relebactam Meropenem-Vaborbactam:两个小说Carbapenem-beta-Lactamase抑制剂的组合。

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Zhanel GG,劳伦斯CK,亚当·H F施魏策尔,Zelenitsky年代,Zhanel M, Lagace-Wiens PRS, Walkty, Denisuik,金色,杜松子酒,贺朋的DJ,林奇JP 3日Karlowsky农协

Imipenem-Relebactam Meropenem-Vaborbactam:两个小说Carbapenem-beta-Lactamase抑制剂的组合。

药。2018年1月,78 (1):65 - 98。doi: 10.1007 / s40265 - 017 - 0851 - 9。

PubMed ID

29230684 (在PubMed

]

文摘

Relebactam(以前称为mk - 7655)是一个non-beta-lactam,二环diazabicyclooctane, beta-lactamase抑制剂avibactam结构相关,不同的两位羰基哌啶环。Vaborbactam(原名RPX7009)是一个non-beta-lactam,循环,boronic酸碱度,beta-lactamase抑制剂。vaborbactam的结构不同于其他任何目前销售beta-lactamase抑制剂。两种抑制剂显示活动反对Ambler类(包括extended-spectrum beta-lactamases (ESBLs),肺炎克雷伯菌"(组织)]和C类beta-lactamases (AmpC)。对潜在的阻力relebactambeplayapp或vaborbactam选择;然而,孔蛋白的失活蛋白质OmpK36 k .肺炎报道imipenem-relebactam和meropenem-vaborbactam带来阻力。添加relebactam显著提高imipenem对肠杆菌科的大部分物种的活动(通过降低最低抑制浓度(MIC) 2 - 128倍)取决于beta-lactamase酶的存在与否。对铜绿假单胞菌,增加relebactam也提高的活动imipenem(麦克风减少8倍)。基于数据,添加relebactam并不能提高的活动imipenem对鲍曼不动杆菌,Stenotrophomonas maltophilia和大多数厌氧菌。imipenem-relebactam相似,添加vaborbactam显著(2 - > 1024倍减少麦克风)改善meropenem对肠杆菌科的大部分物种的活动取决于beta-lactamase酶的存在与否。 Limited data suggest that the addition of vaborbactam does not improve the activity of meropenem against A. baumannii, P. aeruginosa, or S. maltophilia. The pharmacokinetics of both relebactam and vaborbactam are described by a two-compartment, linear model and do not appear to be altered by the co-administration of imipenem and meropenem, respectively. Relebactam's approximate volume of distribution (V d) and elimination half-life (t (1/2)) of ~ 18 L and 1.2-2.1 h, respectively, are similar to imipenem. Likewise, vaborbactam's V d and t(1/2) of ~ 18 L and 1.3-2.0 h, respectively, are comparable to meropenem. Like imipenem and meropenem, relebactam and vaborbactam are both primarily renally excreted, and clearance correlates with creatinine clearance. In vitro and in vivo pharmacodynamic studies have reported bactericidal activity for imipenem-relebactam and meropenem-vaborbactam against various Gram-negative beta-lactamase-producing bacilli that are not inhibited by their respective carbapenems alone. These data also suggest that pharmacokinetic-pharmacodynamic parameters correlating with efficacy include time above the MIC for the carbapenems and overall exposure for their companion beta-lactamase inhibitors. Phase II clinical trials to date have reported that imipenem-relebactam is as effective as imipenem alone for treatment of complicated intra-abdominal infections and complicated urinary tract infections, including acute pyelonephritis. Imipenem-relebactam is currently in two phase III clinical trials for the treatment of imipenem-resistant bacterial infections, as well as hospital-associated bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). A phase III clinical trial has reported superiority of meropenem-vaborbactam over piperacillin-tazobactam for the treatment of complicated urinary tract infections, including acute pyelonephritis. Meropenem-vaborbactam has recently demonstrated higher clinical cure rates versus best available therapy for the treatment of carbapenem-resistant Enterobacteriaceae (CRE), as well as for HABP and VABP. The safety and tolerability of imipenem-relebactam and meropenem-vaborbactam has been reported in various phase I pharmacokinetic studies and phase II and III clinical trials. Both combinations appear to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date. In conclusion, relebactam and vaborbactam serve to broaden the spectrum of imipenem and meropenem, respectively, against beta-lactamase-producing Gram-negative bacilli. The exact roles for imipenem-relebactam and meropenem-vaborbactam will be defined by efficacy and safety data from further clinical trials. Potential roles in therapy for these agents include the treatment of suspected or documented infections caused by resistant Gram-negative bacilli-producing ESBL, KPC, and/or AmpC beta-lactamases. The usage of these agents in patients with CRE infections will likely become the standard of care. Finally, increased activity of imipenem-relebactam against P. aeruginosa may be of clinical benefit to patients with suspected or documented P. aeruginosa infections.

beplay体育安全吗DrugBank数据引用了这篇文章

药物

Relebactam

药物靶点

药物	目标	类	生物	药理作用	行动
Relebactam	Beta-lactamase	蛋白质	肠杆菌属下水道	是的	抑制剂	细节
Relebactam	Beta-lactamase (KPC-2)	蛋白质	肺炎克雷伯菌	是的	抑制剂	细节
Relebactam	Beta-lactamase CTX-M(蛋白质组)	蛋白质组	大肠杆菌	是的	抑制剂	细节
Relebactam	Beta-lactamase SHV-1	蛋白质	大肠杆菌	是的	抑制剂	细节
Relebactam	Beta-lactamase TEM	蛋白质	大肠杆菌	是的	抑制剂	细节