Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, People's Republic of China.
Emerg Microbes Infect. 2024 Dec;13(1):2332658. doi: 10.1080/22221751.2024.2332658. Epub 2024 Apr 3.
Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains ( < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups ( < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.
耐碳青霉烯肠杆菌科细菌（CRE），特别是对碳青霉烯类药物中仅厄他培南耐药的（ETP 单耐药）CRE 越来越多，而最佳治疗选择仍不确定。为了研究 ETP 单耐药 CRE 的流行情况和特征，我们从 2018 年至 2021 年在全国 102 家医院系统收集了 CRE 菌株。对 ETP 单耐药菌株与美罗培南和/或亚胺培南耐药（MEM/IPM 耐药）菌株进行了 1:1 随机匹配研究。测定了抗菌药物敏感性试验、全基因组测序、碳青霉烯水解活性和碳青霉烯酶基因的表达。总共 18.8%的 CRE 菌株为 ETP 单耐药，厄他培南 MIC 值相对较低。ETP 单耐药菌株对β-内酰胺类、β-内酰胺/β-内酰胺酶抑制剂合剂、左氧氟沙星、磷霉素、阿米卡星和多粘菌素的敏感性增强（<0.05）。系统发育分析显示 ETP 单耐药菌株具有较高的遗传多样性。发现扩展谱β-内酰胺酶（ESBLs）和/或 AmpC 以及孔蛋白突变是介导 ETP 单耐药的潜在主要机制，而碳青霉烯酶的存在是区分两组之间碳青霉烯耐药表型的关键因素（<0.001）。与 MEM/IPM 耐药组相比，ETP 单耐药组中有限的产碳青霉烯酶 CRE（CP-CRE）菌株的 ESBLs 和孔蛋白突变的发生率显著较低，同时碳青霉烯酶的表达降低。值得注意的是，斑点试验结合改良的碳青霉烯灭活方法表明，ETP 单耐药 CP-CRE 分离株在美罗培南浓度比其相应 MIC 值高 8 倍的情况下仍能生长，同时迅速增强了碳青霉烯水解能力。这些发现表明，ETP 单耐药 CRE 菌株相对流行，在单独使用美罗培南治疗时应谨慎。应优先检测碳青霉烯酶。
