Zhu Yiwei, Chen Jie, Shen Han, Chen Zhongju, Yang Qi-Wen, Zhu Jin, Li Xi, Yang Qing, Zhao Feng, Ji Jingshu, Cai Heng, Li Yue, Zhang Linghong, Leptihn Sebastian, Hua Xiaoting, Yu Yunsong
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang Universitygrid.13402.34 School of Medicine, Hangzhou, China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.
mSystems. 2021 Dec 21;6(6):e0078721. doi: 10.1128/mSystems.00787-21. Epub 2021 Nov 2.
Klebsiella pneumoniae carbapenemase (KPC)-producing Pseudomonas aeruginosa (KPC-PA) has been reported sporadically. However, epidemiological and antimicrobial susceptibility data specific for KPC-PA are lacking. We collected 374 carbapenem-resistant P. aeruginosa (CRPA) isolates from seven hospitals in China from June 2016 to February 2019 and identified the gene in 40.4% ( = 151/374) of the isolates. Approximately one-half of all KPC-PA isolates ( = 76/151; 50.3%) were resistant to ceftazidime-avibactam (CAZ-AVI). Combining Kraken2 taxonomy identification and Nanopore sequencing, we identified eight plasmid types, five of which carried , and 13 combination patterns of these plasmid types. In addition, we identified IS-ΔTn and Tn-like-ΔTn as the two mobile genetic elements that mediated transmission. plasmid curing in 28 strains restored CAZ-AVI susceptibility, suggesting that was the mediator of CAZ-AVI resistance. Furthermore, the copy number was found to correlate with KPC expression and, therefore, CAZ-AVI resistance. Taken together, our results suggest that KPC-PA is becoming a clinical threat and that using CAZ-AVI to treat this specific pathogen should be done with caution. Previous research has reported several cases of KPC-PA strains and three KPC-encoding P. aeruginosa plasmid types in China. However, the prevalence and clinical significance of KPC-PA are not available. In addition, the susceptibility of the strains to CAZ-AVI remains unknown. Samples in this study were collected from seven tertiary hospitals prior to CAZ-AVI clinical approval in China. Therefore, our results represent a retrospective study establishing the baseline efficacy of the novel β-lactam/β-lactamase combination agent for treating KPC-PA infections. The observed correlation between the copy number and CAZ-AVI resistance suggests that close monitoring of the susceptibility of the strain during treatment is required. It would also be beneficial to screen for the gene in CRPA strains for antimicrobial surveillance purposes.
产肺炎克雷伯菌碳青霉烯酶（KPC）的铜绿假单胞菌（KPC-PA）已有零星报道。然而，缺乏针对KPC-PA的流行病学和抗菌药物敏感性数据。我们从2016年6月至2019年2月期间从中国七家医院收集了374株耐碳青霉烯铜绿假单胞菌（CRPA）分离株，并在40.4%（n = 151/374）的分离株中鉴定出该基因。所有KPC-PA分离株中约一半（n = 76/151；50.3%）对头孢他啶-阿维巴坦（CAZ-AVI）耐药。结合Kraken2分类鉴定和纳米孔测序，我们鉴定出八种质粒类型，其中五种携带该基因，以及这些质粒类型的13种组合模式。此外，我们鉴定出IS-ΔTn和Tn样-ΔTn作为介导该基因传播的两种移动遗传元件。对28株菌株进行质粒消除恢复了对CAZ-AVI的敏感性，表明该基因是CAZ-AVI耐药的介导因素。此外，发现该基因的拷贝数与KPC表达相关，因此与CAZ-AVI耐药相关。综上所述，我们的结果表明KPC-PA正成为一种临床威胁，使用CAZ-AVI治疗这种特定病原体时应谨慎。先前的研究报道了中国几例KPC-PA菌株病例和三种编码KPC的铜绿假单胞菌质粒类型。然而，KPC-PA的流行情况和临床意义尚不清楚。此外，这些菌株对CAZ-AVI的敏感性仍然未知。本研究中的样本是在中国临床批准CAZ-AVI之前从七家三级医院收集的。因此，我们的结果代表了一项回顾性研究，确立了新型β-内酰胺/β-内酰胺酶联合制剂治疗KPC-PA感染的基线疗效。观察到的该基因拷贝数与CAZ-AVI耐药之间的相关性表明，在治疗期间需要密切监测菌株的敏感性。为了进行抗菌监测，在CRPA菌株中筛查该基因也将是有益的。
