对头孢他啶/阿维巴坦、美罗培南/瓦博巴坦和亚胺培南/乐巴坦耐药的移植患者携带KPC-245变异肺炎克雷伯菌新菌株的全基因组测序特征

IF 3.7 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-03-18 DOI:10.1016/j.jgar.2025.03.006

Claudia Vaiana , Roberta Vazzana , Salvatore Castelbuono , Andrea Cona , Alessandra Mularoni , Rita Minucci , Francesco Monaco , Daniele Di Carlo , Pier Giulio Conaldi , Alessia Gallo , Nicola Cuscino

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引用次数: 0

摘要

目的：近几十年来，携带多药耐药kpc的肺炎克雷伯菌（KPC-Kp）的日益流行已成为全球公众关注的问题。在此，我们鉴定了一株从危重移植患者分离的头孢他啶/阿维巴坦（CAZ/AVI）、美罗培南/瓦博巴坦（MER-VAB）和亚胺培南/瑞巴坦（IMI-REL）耐药KPC-Kp菌株。方法：采用药敏试验和全基因组测序（WGS）对菌株进行表型和基因型鉴定。基因组DNA测序使用Illumina平台。生物信息学分析用于研究抗性和毒力特征的基因组序列，以及质粒的表征。结果：表型鉴定显示，KPC-Kp分离物对多种抗生素具有高度耐药性，包括所有β -内酰胺/ β -内酰胺酶抑制剂组合，如CAZ/AVI、MER-VAB、IMI-REL和头孢地罗（FDC）。WGS分析表明，该分离株属罕见的ST661株，含有多个抗性和毒力基因。在这些抗性基因中，我们发现了一个新的KPC变体，位于移动遗传元件Tn4401内，KPC-245，其特征是在263位插入9个氨基酸（RAPNKDDYT），与KPC-3相比，蛋白质序列的氨基酸变化为E274D。有趣的是，仅在blaKPC基因中存在突变，而在其他β -内酰胺酶编码基因中不存在突变，这强烈表明KPC-245在β -内酰胺/ β -内酰胺酶抑制剂联合使用和FDC耐药中起作用。结论：在我们的研究中，通过对临床分离物的WGS分析，我们在Tn4401转座子内发现了一个新的blaKPC变体。我们的研究结果证实了持续监测耐多药肺炎克雷伯菌在临床中的重要作用。

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Whole-genome sequencing characterisation of a new KPC-245 variant-carrying Klebsiella pneumoniae strain isolated from a transplanted patient and resistant to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam

Objective

In recent decades, the increasing prevalence of multidrug-resistant Klebsiella pneumoniae carbapenemase (KPC)-carrying K. pneumoniae (KPC-Kp) has become a worldwide public concern. Herein, we characterised a ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER/VAB) and imipenem/relebactam (IMI/REL)-resistant KPC-Kp strain isolated from a critically ill transplant patient.

Methods

Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were conducted to characterise the strain at phenotypic and genotypic levels. Genomic DNA was sequenced using the Illumina platform. Bioinformatic analyses were used to investigate the genome sequences both for resistance and virulence features, and for the characterisation of plasmids.

Results

Phenotypic characterisation revealed that the KPC-Kp isolate was highly resistant to a wide range of antibiotics, including all β-lactam/β-lactamase inhibitor combinations such as CAZ/AVI, MER/VAB, IMI/REL and cefiderocol. WGS analysis showed that the isolate, belonging to the rare lineage ST661, contained several resistance and virulence genes. Among the resistance genes, we identified a new KPC variant within the mobile genetic element Tn4401—KPC-245—characterised by the insertion of nine amino acids (RAPNKDDYT) at position 263 as well as an amino acid change within the protein sequence, E274D, compared with KPC-3. Interestingly, the presence of mutations only in the bla_KPC gene and not in other β-lactamase coding genes strongly points to the role of KPC-245 in β-lactam/β-lactamase inhibitor combinations and cefiderocol resistance.

Conclusions

In our study, by using WGS analysis on a clinical isolate, we identified a new bla_KPC variant within the Tn4401 transposon. Our results confirm the importance of continuous surveillance of multidrug-resistant K. pneumoniae in the clinical context.

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来源期刊

Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

8.70

自引率

2.20%

发文量

285

审稿时长

34 weeks

期刊介绍： The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.