International Health Management Associates, Inc., Schaumburg, Illinois, USA
The Medicines Company, San Diego, California, USA.
Antimicrob Agents Chemother. 2017 Dec 21;62(1). doi: 10.1128/AAC.01904-17. Print 2018 Jan.
Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC from 32 to 0.06 μg/ml and the MIC from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent activity against a worldwide collection of clinical isolates of KPC-positive collected in 2014 and 2015.
沃博巴坦（以前称为 RPX7009）是一种新型丝氨酸β-内酰胺酶抑制剂，包括 Ambler 类 A 碳青霉烯酶，如 KPC。本研究采用临床和实验室标准协会（CLSI）标准肉汤微量稀释法，评估了美罗培南-沃博巴坦合剂对 2014 年和 2015 年收集的 991 株 KPC 阳性 分离株的活性。当用固定浓度的 8μg/ml 沃博巴坦检测时，KPC 阳性 分离株对美罗培南的 MIC 为 1μg/ml，MIC 值范围为≤0.03 至>32μg/ml；99.0%（981/991）的分离株对美罗培南-沃博巴坦的 MIC 值为≤4μg/ml，这是美国 FDA 批准的美罗培南-沃博巴坦（Vabomere）敏感性 MIC 折点。沃博巴坦将美罗培南的 MIC 从 32 降至 0.06μg/ml，将 MIC 从>32 降至 1μg/ml。当按 KPC 变异型对分离株进行分层时，美罗培南-沃博巴坦的活性没有差异。我们得出结论，美罗培南-沃博巴坦对 2014 年和 2015 年收集的全球范围内的 KPC 阳性 临床分离株具有很强的抗菌活性。
