Clinical characteristic analysis and detection of bla KPC gene subtype variations in ST11-KL64 CRKP isolates based on whole genome sequencing
10.3760/cma.j.cn114452-20241130-00654
- VernacularTitle:基于全基因组测序的ST11-KL64型CRKP菌株bla KPC基因亚型变异检测及临床特征分析
- Author:
Chengcheng MA
1
;
Na WANG
;
Yuanli DUAN
;
Rongrong YAN
;
Tao YAN
;
Qiuyan WANG
;
Xuan TENG
;
Kexue YU
;
Zhou LIU
Author Information
1. 安徽医科大学第二附属医院检验科，合肥 230601
- Publication Type:Journal Article
- Keywords:
Klebsiella pneumoniae;
Carbapenems;
Beta-lactamases;
Whole genome sequencing;
Ceftazidime/avibactam
- From:
Chinese Journal of Laboratory Medicine
2025;48(9):1172-1178
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.
