In Vitro Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program)
In Vitro Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program)
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DOI：
10.1128/aac.02209-16
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发表时间：
2017-06-01
影响因子：
4.9
通讯作者：
Sahm, Daniel F.
中科院分区：
文献类型：
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作者：
Lob, Sibylle H.;Hackel, Meredith A.;Sahm, Daniel F.
Relebactam（以前称为 MK-7655）是 A 类和 C 类 β-内酰胺酶的抑制剂，包括肺炎克雷伯菌碳青霉烯酶 (KPC)，目前正在与亚胺培南-西司他丁联合进行临床开发。使用临床和实验室标准研究所 (CLSI) 定义的肉汤微量稀释方法，我们评估了亚胺培南-瑞莱巴坦、亚胺培南和七种常规测试的肠外抗菌剂对革兰氏阴性 ESKAPE 病原体（包括肺炎克雷伯菌，n = 689；鲍曼不动杆菌，n = 72；铜绿假单胞菌，n = 845；和肠杆菌）的体外活性。 spp.，n = 399）由美国 21 个临床实验室于 2015 年提交，作为 SMART（抗菌素耐药性趋势监测研究）全球监测计划的一部分。 Relebactam 以 4 = mu g/ml 的固定浓度与双倍稀释的亚胺培南组合进行测试。使用 CLSI 亚胺培南断点解释亚胺培南-瑞巴坦 MIC。铜绿假单胞菌对亚胺培南瑞莱巴坦和亚胺培南的敏感性分别为94.2%（796/845）和70.3%（594/845），肺炎克雷伯菌为99.0%（682/689）和96.1%（662/689），肺炎克雷伯菌为100%（399/399）和100%（399/399）。肠杆菌属 98.0% (391/399) Relebactam 将亚胺培南不敏感的铜绿假单胞菌、肺炎克雷伯菌和肠杆菌菌株的亚胺培南敏感性恢复至 80.5% (202/251)、74.1% (20/27) 和 100% (8/8)。 Relebactam 不会增加不动杆菌属的分离株数量。对亚胺培南敏感，并且对该病原体测试的所有药物的耐药率> 30%。鉴于瑞来巴坦已被证明能够恢复亚胺培南针对当前临床分离的对碳青霉烯类不敏感的肠杆菌科和铜绿假单胞菌的活性，并且其作为治疗抗菌药物耐药性革兰氏阴性菌感染患者的潜力，因此亚胺培南-瑞来巴坦的进一步开发是有必要的。
Relebactam (formerly MK-7655) is an inhibitor of class A and C beta-lactamases, including Klebsiella pneumoniae carbapenemase (KPC), and is currently in clinical development in combination with imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated the in vitro activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (including Klebsiella pneumoniae, n = 689; Acinetobacter baumannii, n = 72; Pseudomonas aeruginosa, n = 845; and Enterobacter spp., n = 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 = mu g/ml in combination with doubling dilutions of imipenem. Imipenem-relebactam MICs were interpreted using CLSI imipenem breakpoints. The respective rates of susceptibility to imipenem-relebactam and imipenem were 94.2% (796/845) and 70.3% (594/845) for P. aeruginosa, 99.0% (682/689) and 96.1% (662/689) for K. pneumoniae, and 100% (399/399) and 98.0% (391/399) for Enterobacter spp. Relebactam restored imipenem susceptibility to 80.5% (202/251), 74.1% (20/27), and 100% (8/8) of isolates of imipenem-nonsusceptible P. aeruginosa, K. pneumoniae, and Enterobacter spp. Relebactam did not increase the number of isolates of Acinetobacter spp. susceptible to imipenem, and the rates of resistance to all of the agents tested against this pathogen were > 30%. Further development of imipenem-relebactam is warranted given the demonstrated ability of relebactam to restore the activity of imipenem against current clinical isolates of Enterobacteriaceae and P. aeruginosa that are nonsusceptible to carbapenems and its potential as a therapy for treating patients with antimicrobial-resistant Gram-negative infections.