Vaborbactam (RPX7009) is a broad-spectrum β-lactamase inhibitor with particularly potent activity against KPC, CTX-M, SHV, and CMY enzymes[1]. Vaborbactam is a cyclic boronic acid pharmacophore β-lactamase competitive inhibitor used to treat complicated urinary tract infections[2]. Vaborbactam forms a reversible coordination bond with β-lactamases and is not hydrolyzed by β-lactamases[3]. Vaborbactam can enhance the activity of β-lactams against Mycobacterium abscessus[4]. Vaborbactam is often used in combination with Meropenem and has potent in vitro activity against resistant Gram-negative pathogens, especially Klebsiella pneumoniae that produces Klebsiella pneumoniae carbapenemase (KPC), with MIC50 values typically ≤ 0.06µg/ml[5].
In vivo, vaborbactam (6.25-100mg/kg) was injected intraperitoneally in mice to treat a 24-hour thigh infection model of Klebsiella pneumoniae KP1094. Combining it with two meropenem regimens (100 and 300mg/kg) produced a dose-dependent bactericidal effect, with a maximum bactericidal effect of 2.50 log CFU/thigh[6].
References:
[1] Hamrick J C, Docquier J D, Uehara T, et al. VNRX-5133 (taniborbactam), a broad-spectrum inhibitor of serine-and metallo-β-lactamases, restores activity of cefepime in Enterobacterales and Pseudomonas aeruginosa[J]. Antimicrobial Agents and Chemotherapy, 2020, 64(3): 10.1128/aac. 01963-19.
[2] Iqbal Z, Sun J, Yang H, et al. Recent developments to cope the antibacterial resistance via β-lactamase inhibition[J]. Molecules, 2022, 27(12): 3832.
[3] Bookser B C, Reddy K R, Boyer S H, et al. Vaborbactam (in Combination with Meropenem as Vabomere), a Non‐β‐Lactam β‐Lactamase Inhibitor for Treatment of Complicated Urinary Tract Infections and Pyelonephritis[J]. Current Drug Synthesis, 2022: 17-40.
[4] Sanchez L, Bitar M, Herail Q, et al. In vitro and intracellular activity of vaborbactam combined with β-lactams against Mycobacterium abscessus[J]. Journal of Antimicrobial Chemotherapy, 2024, 79(8): 1914-1918.
[5] Wenzler E, Scoble P J. An appraisal of the pharmacokinetic and pharmacodynamic properties of meropenem-vaborbactam[J]. Infectious Diseases and Therapy, 2020, 9(4): 769-784.
[6] Sabet M, Tarazi Z, Nolan T, et al. Activity of meropenem-vaborbactam in mouse models of infection due to KPC-producing carbapenem-resistant Enterobacteriaceae[J]. Antimicrobial Agents and Chemotherapy, 2018, 62(1): 10.1128/aac. 01446-17.
Vaborbactam（RPX7009）是一种广谱β-内酰胺酶抑制剂，对KPC、CTX-M、SHV和CMY酶具有特别强效的活性[1]。Vaborbactam是一种环状硼酸药效团β-内酰胺酶竞争性抑制剂，用于治疗复杂的尿路感染[2]。Vaborbactam通过与β-内酰胺酶形成可逆配价键，不会被β-内酰胺酶水解[3]。Vaborbactam可以提高β-内酰胺对抗脓肿分枝杆菌的活性[4]。Vaborbactam通常与Meropenem联合使用，对耐药革兰氏阴性病原体，特别是产生肺炎克雷伯菌碳青霉烯酶（KPC）的肺炎克雷伯菌具有有效的体外活性，MIC50值通常≤ 0.06µg/ml[5]。
在体内，Vaborbactam（6.25-100mg/kg）通过腹腔注射治疗肺炎克雷伯菌 KP1094建立的24小时大腿感染模型小鼠，联合两种美罗培南方案（100和300 mg/kg）均可产生剂量依赖性杀菌效果，最大杀菌效果为2.50 log CFU/大腿[6]。