Lee Jia-Arng, Kuo Yao-Wen, Du Shin-Hei, Lee Tai-Fen, Liao Chun-Hsing, Huang Yu-Tsung, Hsueh Po-Ren
Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Eur J Clin Microbiol Infect Dis. 2025 Feb;44(2):251-262. doi: 10.1007/s10096-024-04993-7. Epub 2024 Nov 18.
This study aimed to investigate the genetic and clinical characteristics of carbapenem-resistant Enterobacterales (CRE) isolates carrying metallo-β-lactamases (MBLs) genes.
A total of 146 non-duplicated isolates of CRE were collected in 2022. Their ceftazidime/avibactam (CZA) susceptibilities were determined using the E test. The phenotypic identification of carbapenemases was conducted using the modified carbapenem inactivation method, followed by sequencing of the five common carbapenemase genes (bla, bla, bla, bla, and bla). Multilocus sequence typing of selected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae complex isolates were performed.
Among the 146 CRE isolates, 52 (35.6%) were resistant to CZA. MBL-encoding genes were detected in 46 (31.5%) of all tested CRE isolates, with 82.6% (n = 38) of them exhibiting resistance to CZA. Fourteen isolates were resistant to CZA without any detected MBL genes. The most commonly identified MBL genes were bla (n = 20), followed by bla (n = 19), and bla (n = 5). In CZA-R, the most common definite antibiotic before the CZA E test was CZA (n = 18), followed by tigecycline (n = 13), and fluroquinolone (n = 10). The 14-day and 30-day mortality rates were 9.0% (n = 13) and 22.8% (n = 34), and were associated with intensive care unit admission at onset (P = 0.029 and P = 0.001, respectively). The sequence types of CRE isolates carrying MBLs were diverse without major clones.
The continuous emergence of MBL gene-encoding CRE with multiple clones has led to reduced CZA susceptibilities and worse outcomes.
本研究旨在调查携带金属β-内酰胺酶(MBLs)基因的耐碳青霉烯类肠杆菌科细菌(CRE)分离株的遗传和临床特征。
2022年共收集了146株非重复的CRE分离株。使用E试验测定其头孢他啶/阿维巴坦(CZA)敏感性。采用改良碳青霉烯灭活法进行碳青霉烯酶的表型鉴定,随后对五个常见碳青霉烯酶基因(bla、bla、bla、bla和bla)进行测序。对选定的肺炎克雷伯菌、大肠埃希菌和阴沟肠杆菌复合体分离株进行多位点序列分型。
在146株CRE分离株中,52株(35.6%)对CZA耐药。在所有测试的CRE分离株中,46株(31.5%)检测到MBL编码基因,其中82.6%(n = 38)对CZA耐药。14株分离株对CZA耐药,但未检测到任何MBL基因。最常见的MBL基因是bla(n = 20),其次是bla(n = 19)和bla(n = 5)。在CZA耐药株中,CZA E试验前最常见的确定抗生素是CZA(n = 18),其次是替加环素(n = 13)和氟喹诺酮(n = 10)。14天和30天死亡率分别为9.0%(n = 13)和22.8%(n = 34),且与发病时入住重症监护病房有关(P分别为0.029和0.001)。携带MBLs的CRE分离株的序列类型多样,无主要克隆。
携带MBL基因的CRE多克隆不断出现,导致CZA敏感性降低,预后更差。