Microbiome and resistome characterization of patients colonized with carbapenem-resistant Enterobacterales by long-read metagenomic next-generation sequencing of rectal swabs.

IF 3.3 Q2 INFECTIOUS DISEASES
JAC-Antimicrobial Resistance Pub Date : 2025-08-28 eCollection Date: 2025-08-01 DOI:10.1093/jacamr/dlaf152
John A Fissel, Yehudit Bergman, Victoria L Campodónico, Dana M Walsh, Brian Fanelli, Keshav Arogyaswamy, Jennie H Kwon, Aaron M Milstone, Pranita D Tamma, Patricia J Simner
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引用次数: 0

Abstract

Objectives: Evaluation of differences in the intestinal microbiome and resistome among high-risk patients (i.e. intensive care, oncology, transplant recipients) who are and are not colonized with carbapenem-resistant Enterobacterales (CRE).

Methods: One hundred and twelve rectal swabs were obtained from 85 patients with known CRE colonization status and cohorted. Long-read metagenomic next-generation sequencing (mNGS) was performed on rectal swabs. Microbiome and resistome analysis were performed by assessing α-diversity, β-diversity, relative abundance assessment and linear discriminant analysis effect size (LEfSe), comparing patients colonized (CRE positive) and not colonized (CRE negative) with CRE. Longitudinal analysis of sequential swabs collected over multiple hospital encounters on a subset of patients was performed at the patient level.

Results: The microbiomes of cohorts were similar when comparing α- and β-diversity measures and relative abundance. LEfSe analysis identified Gram-negative pathobionts enriched among CRE-positive samples and Gram-positive taxa enriched among CRE-negative samples. α-Diversity of the resistome differed at class, gene and allele levels. Relative abundance and LEfSe analysis demonstrated enrichment of genes conferring β-lactam resistance among CRE-positive patients; LEfSe also demonstrated enrichment of antimicrobial resistance genes to multiple antimicrobial classes. At the patient level, fluctuations in the microbiome and resistome among longitudinally collected swabs were associated with antibiotic exposure.

Conclusions: Differences between the microbiomes of CRE-positive- and CRE-negative-colonized patients at the cohort level were relatively muted, whereas statistically significant differences were observed among their resistomes. In patients followed longitudinally, shifts in microbiome and resistome composition were dramatic in between encounters and antibiotic exposures.

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通过直肠拭子长读宏基因组新一代测序研究耐碳青霉烯肠杆菌定植患者的微生物组和抗性组特征
目的:评估存在和未存在碳青霉烯耐药肠杆菌(CRE)定植的高危患者(即重症监护患者、肿瘤患者、移植患者)肠道微生物组和抵抗组的差异。方法:从85例已知CRE定植状态的患者中获得112份直肠拭子,并进行队列分析。对直肠拭子进行长读元基因组下一代测序(mNGS)。通过α-多样性、β-多样性、相对丰度评估和线性判别分析效应大小(LEfSe)进行微生物组和抵抗组分析,比较CRE定植(CRE阳性)和未定植(CRE阴性)患者与CRE的差异。在患者水平上,对在多次医院就诊期间收集的一部分患者的连续拭子进行纵向分析。结果:在比较α-和β-多样性测量和相对丰度时,队列的微生物组相似。LEfSe分析发现,革兰氏阴性病原体在cre阳性样本中富集,革兰氏阳性分类群在cre阴性样本中富集。α-抗性组的多样性在类别、基因和等位基因水平上存在差异。相对丰度和LEfSe分析显示,cre阳性患者中β-内酰胺耐药基因富集;LEfSe还显示了对多种抗菌药物的耐药基因的富集。在患者水平上,纵向收集的拭子中微生物组和抵抗组的波动与抗生素暴露有关。结论:在队列水平上,cre阳性和cre阴性定殖患者的微生物组差异相对较小,而其抗性组之间存在统计学上的显著差异。在纵向随访的患者中,在接触和抗生素暴露之间,微生物组和抵抗组组成的变化是戏剧性的。
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来源期刊
CiteScore
5.30
自引率
0.00%
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审稿时长
16 weeks
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