Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
J Antimicrob Chemother. 2018 Oct 1;73(10):2789-2796. doi: 10.1093/jac/dky251.
Vaborbactam is a novel inhibitor of serine β-lactamases, including KPCs, which predominate in China. It is being developed in combination with meropenem.
Using the broth microdilution method, the in vitro activity of meropenem/vaborbactam against 128 KPC-producing Enterobacteriaceae from China was investigated.
Meropenem alone showed no activity (MIC50 and MIC90 >64 mg/L), but the addition of vaborbactam potentiated meropenem in a dose-dependent manner with MIC90 decreasing from >64 to 0.5 mg/L in the presence of increasing concentrations of vaborbactam. MIC50 and MIC90 of meropenem with 8 mg/L vaborbactam (MV8) were reduced to 0.5 and 8 mg/L, respectively. MV8 (4 mg/L meropenem) inhibited 76.6% of Klebsiella pneumoniae and 100% of Escherichia coli isolates. Seventy-three (77.7%) of the K. pneumoniae isolates belonged to ST11; the remaining 22.3% of isolates were represented by 12 different STs. Of the ST11 and non-ST11 isolates, 71.2% and 95.2%, respectively, were inhibited by MV8 (4 mg/L meropenem). In 14 strains characterized for intrinsic resistance mechanisms, MV8 MIC was increased in isolates with defects in both OmpK35 and OmpK36. The highest MV8 MIC was observed in the strain that had both non-functional porins and increased expression of blaKPC and acrB.
Our findings suggest that meropenem/vaborbactam has good activity against KPC-producing Enterobacteriaceae from China. However, a higher percentage of K. pneumoniae isolates for which MV8 MIC was elevated compared with other geographical areas is noteworthy. This might be due to clonal dissemination of ST11 KPC-producing isolates that are defective in both major porins, OmpK35 and OmpK36.
沃博巴坦是一种新型丝氨酸β-内酰胺酶抑制剂，包括在中国占主导地位的 KPC。它正在与美罗培南联合开发。
采用肉汤微量稀释法，检测了 128 株来自中国的产 KPC 肠杆菌科细菌对美罗培南/沃博巴坦的体外活性。
美罗培南单独使用时无活性（MIC50 和 MIC90＞64mg/L），但随着沃博巴坦浓度的增加，美罗培南的活性呈剂量依赖性增强，MIC90 从＞64mg/L 降低至 0.5mg/L。美罗培南与 8mg/L 沃博巴坦（MV8）联合使用时，MIC50 和 MIC90 分别降至 0.5 和 8mg/L。MV8（4mg/L 美罗培南）抑制了 76.6%的肺炎克雷伯菌和 100%的大肠埃希菌分离株。73（77.7%）株肺炎克雷伯菌属于 ST11；其余 22.3%的分离株由 12 个不同的 ST 组成。在 ST11 和非 ST11 分离株中，MV8（4mg/L 美罗培南）分别抑制了 71.2%和 95.2%的分离株。在 14 株特征明确的固有耐药机制的菌株中，MV8 MIC 在同时存在 OmpK35 和 OmpK36 缺陷的菌株中增加。在同时具有无功能孔蛋白和 blaKPC 和 acrB 表达增加的菌株中观察到最高的 MV8 MIC。
我们的研究结果表明，美罗培南/沃博巴坦对来自中国的产 KPC 肠杆菌科细菌具有良好的活性。然而，与其他地理区域相比，美罗培南/沃博巴坦 MIC 升高的肺炎克雷伯菌分离株比例更高，这一点值得注意。这可能是由于同时存在 OmpK35 和 OmpK36 两种主要孔蛋白缺陷的 ST11 产 KPC 分离株的克隆传播所致。
