Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Department of Medicine Microbiome & Pathogen Genomics Core, Columbia University Medical Center, New York, New York, USA.
Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.00573-18. Print 2018 Aug.
Treatment options for carbapenem-resistant (CRE) are limited. While strains harboring account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether the CRE species and antibiotic resistance genotype influence the response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem-cilastatin (IMI). We carried out broth microdilution testing with IMI alone or in the presence of 4 μg/ml REL against 154 clinical isolates collected at a New York City hospital with a high prevalence of organisms carrying , including spp. ( = 96), ( = 44), ( = 1), ( = 9), and spp. ( = 4). Resistance gene profiles and the presence of major porin gene disruptions were ascertained by whole-genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/ml) against 88% of isolates. However, IMI-REL MICs were 4- to 8-fold higher than those for other organisms. Most -positive isolates had IMI-REL MICs of ≤1 μg/ml (88%), including isolates of ST171 (93%) and ST258 (82%). Nineteen isolates had IMI-REL MICs of ≥2 μg/ml, among which 84% harbored and one was positive. Isolates with IMI-REL MICs of ≥2 μg/ml versus those with MICs of ≤1 μg/ml were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%; = 0.04), although most isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates, including high-risk clones, chromosomal factors had an impact on IMI-REL susceptibilities and may contribute to elevated MICs for .
治疗碳青霉烯类耐药肠杆菌科细菌 (CRE) 的选择有限。虽然携带 基因的菌株占大多数 CRE，但最近的证据表明 CRE 的多样性正在增加。我们确定 CRE 物种和抗生素耐药基因型是否会影响新型β-内酰胺酶抑制剂 REL 与亚胺培南-西司他丁（IMI）联合用药的反应。我们对在纽约市一家医院采集的 154 株临床分离株进行肉汤微量稀释试验，这些分离株携带大量 基因，包括 spp.（=96）、 （=44）、 （=1）、 （=9）和 spp.（=4）。通过全基因组测序确定耐药基因谱和主要孔蛋白基因缺失的存在。添加 REL 可将 88%的分离株的 IMI MIC 降低到敏感范围（≤1μg/ml）。然而，与其他生物体相比， IMI-REL MIC 高 4-8 倍。大多数 阳性分离株的 IMI-REL MIC 为≤1μg/ml（88%），包括 ST171（93%）和 ST258（82%）的分离株。19 株分离株的 IMI-REL MIC 为≥2μg/ml，其中 84%携带 ，1 株为 阳性。与 MIC 为≤1μg/ml 的分离株相比，MIC 为≥2μg/ml 的分离株更有可能至少缺失一个孔蛋白基因（42%对 19%； = 0.04），尽管大多数 分离株（67%）的孔蛋白基因完整。总之，虽然 REL 降低了大多数不同 CRE 分离株（包括高危克隆）的 IMI MIC，但染色体因素对 IMI-REL 敏感性有影响，可能导致 的 MIC 升高。
