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一所学术性医学中心及其附属医院血流感染分离株的异质性。

Heterogeneity of bloodstream isolates in an academic medical center and affiliated hospitals.

作者信息

Scott Nancy E, Wash Elizabeth, Zajac Christopher, Erayil Serin E, Kline Susan E, Selmecki Anna

机构信息

Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, Minnesota, USA.

Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.

出版信息

Microbiol Spectr. 2025 Aug 5;13(8):e0046425. doi: 10.1128/spectrum.00464-25. Epub 2025 Jun 23.

DOI:10.1128/spectrum.00464-25
PMID:40548736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12323643/
Abstract

Invasive bloodstream infections (candidemia) are a deadly global health threat. Rare species are becoming increasingly important causes of candidemia. Phenotypic data, including patterns of antifungal drug resistance, are limited. There is a geographic variation in the distribution of species and frequency of antifungal drug resistance, meaning that regional data can have significant clinical value. Here, we report on the species distribution, frequency of antifungal drug resistance, and phenotypic variability of bloodstream isolates from an academic medical center and five affiliated hospitals in the Minneapolis-Saint Paul region of Minnesota collected during an 18-month period from 2019 to 2021. We collected 288 isolates spanning 11 species from 119 patients. was recovered from 45% of cases, followed by (35%), (7%), and (2.5%), with 10% of cases representing additional rare species. We performed antifungal drug susceptibility by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) method for three major drug classes. Concerningly, we identified fluconazole, micafungin, and multidrug resistance rates in that were ~2 times higher than that reported in other regions of the United States. Through analysis of serial isolates from individual patients, we identified clinically relevant within-patient differences of MIC values in multiple drug classes. We also report phenotypic data in rare non-albicans species to address a significant gap in available data. Our results provide valuable clinical data relevant to antifungal stewardship efforts and highlight important areas of future research, including within-patient dynamics of infection and the mechanisms of drug resistance in rare species.IMPORTANCE species are an important cause of hospital-acquired infection. The prevalence of species causing infections and the frequency of antifungal drug resistance have changed over time. Reporting the regional species distribution and phenotypes has clinical significance. Current clinical microbiology practices may underestimate the within-host diversity of infecting strains, including important variation in drug susceptibility. Our study reports the results of an 18-month survey of bloodstream infections in an academic medical center and associated hospitals in the Minneapolis-Saint Paul region of Minnesota. We identified antifungal drug resistance, including multidrug resistance, in multiple non-albicans species. By analyzing serial isolates from individual patients, we identified clinically relevant differences in drug susceptibility during infection. Our results contribute data to antifungal stewardship efforts and identify avenues of future research.

摘要

侵袭性血流感染(念珠菌血症)是一种致命的全球健康威胁。罕见念珠菌属正日益成为念珠菌血症的重要病因。包括抗真菌药物耐药模式在内的表型数据有限。念珠菌属的分布以及抗真菌药物耐药频率存在地域差异,这意味着区域数据可能具有重要的临床价值。在此,我们报告了2019年至2021年18个月期间从明尼苏达州明尼阿波利斯 - 圣保罗地区的一家学术医疗中心和五家附属医院收集的血流感染分离株的菌种分布、抗真菌药物耐药频率及表型变异性。我们从119名患者中收集了288株分离株,涵盖11个菌种。白色念珠菌从45%的病例中分离得到,其次是光滑念珠菌(35%)、近平滑念珠菌(7%)和热带念珠菌(2.5%),10%的病例为其他罕见菌种。我们采用欧洲抗菌药物敏感性试验委员会(EUCAST)的方法对三大类主要药物进行了抗真菌药物敏感性检测。令人担忧的是,我们发现克柔念珠菌对氟康唑、米卡芬净的耐药率以及多重耐药率比美国其他地区报告的高出约2倍。通过分析个体患者的系列分离株,我们在多种药物类别中确定了患者体内具有临床相关性的最低抑菌浓度(MIC)值差异。我们还报告了罕见的非白色念珠菌属菌种的表型数据,以填补现有数据中的重大空白。我们的结果为抗真菌管理工作提供了有价值的临床数据,并突出了未来研究的重要领域,包括患者体内感染动态以及罕见念珠菌属菌种的耐药机制。重要性念珠菌属是医院获得性感染的重要病因。引起感染的念珠菌属菌种流行率以及抗真菌药物耐药频率随时间发生了变化。报告区域念珠菌属菌种分布和表型具有临床意义。当前临床微生物学实践可能低估了感染菌株在宿主体内的多样性,包括药物敏感性的重要差异。我们的研究报告了对明尼苏达州明尼阿波利斯 - 圣保罗地区一家学术医疗中心及相关医院进行的为期18个月的念珠菌血流感染调查结果。我们在多种非白色念珠菌属菌种中发现了抗真菌药物耐药性,包括多重耐药性。通过分析个体患者的系列分离株,我们确定了感染期间药物敏感性的临床相关差异。我们的结果为抗真菌管理工作提供了数据,并确定了未来研究的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b02b/12323643/585d38f48fe7/spectrum.00464-25.f005.jpg
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本文引用的文献

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Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial isolates.患者连续分离株中获得性氟康唑和棘白菌素耐药性的基因组描述。
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Global incidence and mortality of severe fungal disease.全球严重真菌感染的发病率和死亡率。
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Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy.
两性霉素 B 联合米卡芬净治疗肺部毛霉菌病一例
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Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant Candida parapsilosis.全基因组测序证实了多重耐药近平滑念珠菌引起的持续念珠菌血症克隆爆发。
J Antimicrob Chemother. 2023 Jun 1;78(6):1488-1494. doi: 10.1093/jac/dkad112.
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Antifungal Tolerance and Resistance Emerge at Distinct Drug Concentrations and Rely upon Different Aneuploid Chromosomes.抗真菌药物耐受性和耐药性在不同药物浓度下出现,并依赖于不同的非整倍体染色体。
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Macrophage internalization creates a multidrug-tolerant fungal persister reservoir and facilitates the emergence of drug resistance.巨噬细胞内化会产生一个多药耐受真菌持久存贮库,并促进耐药性的出现。
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The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris.新型真菌病原体耳念珠菌的抗真菌耐药性的分子和遗传基础。
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