Menglan Zhou1,2,3, Qiwen Yang1,3, Olga Lomovskaya4, Dongxu Sun4, Timothy Kudinha5,6, Zhipeng Xu1,3, Ge Zhang1,3, Xinxin Chen1,3, Yingchun Xu1,3. 1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 2. Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 3. Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China. 4. The Medicines Company, San Diego, CA, USA. 5. Charles Sturt University, Orange, New South Wales, Australia. 6. Pathology West, Orange, New South Wales, Australia.
Abstract
Background: Vaborbactam is a novel inhibitor of serine β-lactamases, including KPCs, which predominate in China. It is being developed in combination with meropenem. Methods: Using the broth microdilution method, the in vitro activity of meropenem/vaborbactam against 128 KPC-producing Enterobacteriaceae from China was investigated. Results: 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. Conclusions: 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.
Background: Vaborbactam is a novel inhibitor of serine β-lactamases, including KPCs, which predominate in China. It is being developed in combination with meropenem. Methods: Using the broth microdilution method, the in vitro activity of meropenem/vaborbactam against 128 KPC-producing Enterobacteriaceae from China was investigated. Results: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. Conclusions: 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.
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