意大利北部三所大学医院三年来流行的产碳青霉烯酶肺炎克雷伯菌(KPC-Kp)菌株的基因组特征。

IF 4.8 2区 医学 Q1 INFECTIOUS DISEASES
Valeria Fox, Davide Mangioni, Silvia Renica, Agnese Comelli, Antonio Teri, Michela Zatelli, Beatrice Silvia Orena, Cristina Scuderi, Annalisa Cavallero, Marianna Rossi, Maddalena Casana, Ludovica Mela, Alessandra Bielli, Rossana Scutari, Paola Morelli, Lisa Cariani, Erminia Casari, Chiara Silvia Vismara, Caterina Matinato, Annapaola Callegaro, Barbara Bottazzi, Barbara Cassani, Carlo Federico Perno, Andrea Gori, Antonio Muscatello, Alessandra Bandera, Claudia Alteri
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引用次数: 0

摘要

目的:对产碳青霉烯酶肺炎克雷伯菌(KPC-Kp)进行基因组监测对于毒力、耐药性监测和疫情遏制至关重要:通过全基因组测序(WGS)对2019-2021年从意大利北部3家医院分离的87株KPC-Kp菌株进行了基因组分析,以确定耐药基因组、毒力基因组和动员基因组的特征,并评估与表型耐药性和临床表现的潜在关联。最大似然法和最小跨度树用于确定菌株相关性和识别潜在的传播集群:结果:总共发现了 15 种不同的 ST,主要包括 ST307(35 株,占 40.2%)、ST512/1519(15 株,占 17.2%)、ST20(12 株,占 13.8%)和 ST101(7 株,占 8.1%)。33株(37.9%)KPC-Kp菌株被发现分布在5个传播群组中(每个群组中分离株数的中位数:5[3-10]),其中4个群组以院内传播为特征。所有 87 株菌株均携带 Tn4401a 转座子,其中有 48 株(55.2%)携带 blaKPC-3,38 株(43.7%)携带 blaKPC-2,1 株(1.2%)携带 blaKPC-33,后者可产生对头孢他啶/阿维巴坦(CZA)的耐药性。30株菌株(34.5%)携带孔蛋白突变,其中7株(8.1%)携带多个Tn4401a拷贝。这些菌株的特点是,与没有孔蛋白突变或只有一个Tn4401a拷贝的菌株相比,它们的CZA最低抑菌浓度明显更高,即使它们没有突破8微克/毫升的耐药性断点。每个菌株检测到的毒力因子中位数为 2 个(IQR:1-2)。与其他 ST 相比,ST20 的毒力因子数量最少(pConclusions:通过整合基因组、耐药性评分和临床数据,我们确定了 2019 年至 2021 年期间意大利北部 KPC-Kp 的相对多样化,其特点是很少有大型传播链和罕见的医院间传播。我们的研究结果还提供了 KPC-Kp 基因组特征与对某些抗菌药物或定植/感染状态的较高 MIC 水平之间相关性的初步证据,再次强调了 WGS 在细菌监测中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic characterization of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) strains circulating in three university hospitals in Northern Italy over three years.

Objectives: Genomic surveillance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is crucial for virulence, drug-resistance monitoring, and outbreak containment.

Methods: Genomic analysis on 87 KPC-Kp strains isolated from 3 Northern Italy hospitals in 2019-2021 was performed by whole genome sequencing (WGS), to characterize resistome, virulome, and mobilome, and to assess potential associations with phenotype resistance and clinical presentation. Maximum Likelihood and Minimum Spanning Trees were used to determine strain correlations and identify potential transmission clusters.

Results: Overall, 15 different STs were found; the predominant ones included ST307 (35, 40.2%), ST512/1519 (15, 17.2%), ST20 (12, 13.8%), and ST101 (7, 8.1%). 33 (37.9%) KPC-Kp strains were noticed to be in five transmission clusters (median number of isolates in each cluster: 5 [3-10]), four of them characterized by intra-hospital transmission. All 87 strains harbored Tn4401a transposon, carrying blaKPC-3 (48, 55.2%), blaKPC-2 (38, 43.7%), and in one case (1.2%) blaKPC-33, the latter gene conferred resistance to ceftazidime/avibactam (CZA). Thirty strains (34.5%) harbored porin mutations; of them, 7 (8.1%) carried multiple Tn4401a copies. These strains were characterized by significantly higher CZA minimum inhibitory concentration compared with strains with no porin mutations or single Tn4401a copy, respectively, even if they did not overcome the resistance breakpoint of 8 ug/mL. Median 2 (IQR:1-2) virulence factors per strain were detected. The lowest number was observed in ST20 compared to the other STs (p<0.001). While ST307 was associated with infection events, a trend associated with colonization events could be observed for ST20.

Conclusions: Integration of genomic, resistance score, and clinical data allowed us to define a relative diversification of KPC-Kp in Northern Italy between 2019 and 2021, characterized by few large transmission chains and rare inter-hospital transmission. Our results also provided initial evidence of correlation between KPC-Kp genomic signatures and higher MIC levels to some antimicrobial agents or colonization/infection status, once again underlining WGS's importance in bacterial surveillance.

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来源期刊
Antimicrobial Resistance and Infection Control
Antimicrobial Resistance and Infection Control PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.60%
发文量
140
审稿时长
13 weeks
期刊介绍: Antimicrobial Resistance and Infection Control is a global forum for all those working on the prevention, diagnostic and treatment of health-care associated infections and antimicrobial resistance development in all health-care settings. The journal covers a broad spectrum of preeminent practices and best available data to the top interventional and translational research, and innovative developments in the field of infection control.
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