High diversity of strain clonality and metallo-β-lactamases genes among carbapenem-resistant Enterobacterales in Taiwan

Jia-Arng Lee; Yao-Wen Kuo; Shin-Hei Du; Tai-Fen Lee; Chun-Hsing Liao; Yu-Tsung Huang; Po-Ren Hsueh

doi:10.1007/s10096-024-04993-7

High diversity of strain clonality and metallo-β-lactamases genes among carbapenem-resistant Enterobacterales in Taiwan

Eur J Clin Microbiol Infect Dis. 2024 Nov 18. doi: 10.1007/s10096-024-04993-7. Online ahead of print.

Authors

Jia-Arng Lee^{1

2}, Yao-Wen Kuo³, Shin-Hei Du¹, Tai-Fen Lee¹, Chun-Hsing Liao^{4

5}, Yu-Tsung Huang^{6

7}, Po-Ren Hsueh^{8

9

10

11}

Affiliations

¹ Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
² Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
³ Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
⁵ Colleague of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁶ Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. yutsunghuang@gmail.com.
⁷ Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan. yutsunghuang@gmail.com.
⁸ Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. hsporen@gmail.com.
⁹ Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. hsporen@gmail.com.
¹⁰ Ph.D Program for Aging, College of Medicine, China Medical University, Taichung, Taiwan. hsporen@gmail.com.
¹¹ Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. hsporen@gmail.com.

PMID: 39551908
DOI: 10.1007/s10096-024-04993-7

Abstract

Purpose: This study aimed to investigate the genetic and clinical characteristics of carbapenem-resistant Enterobacterales (CRE) isolates carrying metallo-β-lactamases (MBLs) genes.

Methods: 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_KPC, bla_NDM, bla_VIM, bla_IMP, and bla_OXA-48). Multilocus sequence typing of selected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae complex isolates were performed.

Results: 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_IMP (n = 20), followed by bla_NDM (n = 19), and bla_VIM (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.

Conclusion: The continuous emergence of MBL gene-encoding CRE with multiple clones has led to reduced CZA susceptibilities and worse outcomes.

Keywords: Enterobacter cloacae complex; Klebsiella oxytoca; Carbapenem-resistant; Enterobacterales; Metallo-β-lactamases.