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分析患者、医护人员和环境中的重症监护病房耐药基因组动态,以识别脓毒症和早期死亡的预测生物标志物。

Analysis of ICU resistome dynamics in patients, staff and environment for the identification of predictive biomarkers of sepsis and early mortality.

作者信息

Mikolas Maja, Fauszt Peter, Petrilla Annamaria, Nemeth Peter, David Peter, Szilagyi-Tolnai Emese, Szilagyi-Racz Anna, Stagel Aniko, Gal Ferenc, Gal Kristof, Sohajda Reka, Szoke Zsombor, Hossain Syed Akib, Stundl Laszlo, Biro Sandor, Remenyik Judit, Paholcsek Melinda

机构信息

Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Complex Systems and Microbiome-innovations Centre, Debrecen, Hungary.

Central Anesthesiology and Intensive Patient Care Department, Vas County Markusovszky University Teaching Hospital, Szombathely, Hungary.

出版信息

Sci Rep. 2025 Jul 11;15(1):25080. doi: 10.1038/s41598-025-10848-8.

DOI:10.1038/s41598-025-10848-8
PMID:40646273
Abstract

Antimicrobial resistance (AMR) is a global crisis, posing a critical challenge to healthcare systems, particularly in intensive care units (ICUs), where multidrug-resistant organisms (MDROs) threaten patient survival. This study offers a unique, real-world perspective on AMR dynamics by analyzing 96 metagenomic samples from three key sources: oropharyngeal and rectal swabs of deceased ICU patients (both postadmission and antemortem), healthcare workers, and high-touch ICU surfaces. Findings revealed the ICU environment as a major AMR reservoir, with oropharyngeal swabs carrying the highest AMR burden. While healthcare staff facilitated MDRO spread, they were not primary sources. Staff microbiomes' MDRO pattern closely resembled environmental samples. Key AMR species included B. fragilis, E. coli, S. pneumoniae, S. aureus, with P. aeruginosa persisting on high-touch surfaces. Tetracycline resistance was the most prevalent, with common resistances comprising 36.1% of all detected AMR markers. Staff microbial community exhibited higher resistance to macrolides, fluoroquinolones, lincosamides, and cephamycins. A 10-day survival threshold distinguished early (EM) and late mortality (LM) groups. EM patients exhibited unique AMR species in the oropharynx, suggesting respiratory-driven infections, while LM patients showed greater gut-associated resistance. Higher rectal AMR counts correlated with prolonged survival. Notably, four key MDROs (L. monocytogenes, M. tuberculosis, S. haemolyticus, and S. agalactiae) were enriched in sepsis patients, suggesting early risk markers. Fewer new resistances emerged in rectal than oropharyngeal swabs, likely due to antibiotic selection pressure. Vancomycin and levofloxacin, frequently co-administered, exerted stronger selective pressure in the oropharynx, possibly explaining the high MRSA prevalence in patient and environmental samples.

摘要

抗菌药物耐药性(AMR)是一场全球危机,对医疗系统构成了严峻挑战,尤其是在重症监护病房(ICU),多重耐药菌(MDROs)威胁着患者的生存。本研究通过分析来自三个关键来源的96份宏基因组样本,提供了关于AMR动态的独特的现实世界视角:已故ICU患者的口咽和直肠拭子(入院后和死前)、医护人员以及ICU的高接触表面。研究结果显示,ICU环境是主要的AMR储存库,口咽拭子携带的AMR负担最高。虽然医护人员促成了MDRO的传播,但他们不是主要来源。医护人员微生物群的MDRO模式与环境样本非常相似。关键的AMR物种包括脆弱拟杆菌、大肠杆菌、肺炎链球菌、金黄色葡萄球菌,铜绿假单胞菌在高接触表面持续存在。四环素耐药性最为普遍,常见耐药性占所有检测到的AMR标记的36.1%。医护人员的微生物群落对大环内酯类、氟喹诺酮类、林可酰胺类和头孢霉素类表现出更高的耐药性。10天的生存阈值区分了早期死亡(EM)和晚期死亡(LM)组。EM患者在口咽中表现出独特的AMR物种,提示由呼吸道驱动的感染,而LM患者表现出更强的肠道相关耐药性。直肠AMR计数较高与生存期延长相关。值得注意的是,四种关键的MDRO(单核细胞增生李斯特菌、结核分枝杆菌、溶血葡萄球菌和无乳链球菌)在脓毒症患者中富集,提示早期风险标志物。直肠拭子中出现的新耐药性比口咽拭子少,可能是由于抗生素选择压力。经常联合使用的万古霉素和左氧氟沙星在口咽中施加了更强的选择压力,这可能解释了患者和环境样本中耐甲氧西林金黄色葡萄球菌(MRSA)的高流行率。

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本文引用的文献

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Antibiotics (Basel). 2025 Mar 11;14(3):290. doi: 10.3390/antibiotics14030290.
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Impact of healthcare-associated infections on in-hospital outcomes during the COVID-19 era: a multicenter comparative study of 20,942 isolated microorganisms from ICU patients.新冠疫情时代医疗相关感染对住院结局的影响:一项对20942株来自ICU患者的分离微生物的多中心比较研究
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美国成年人口腔微生物群的α多样性与全因死亡率、心血管死亡率和非心血管死亡率:来自2009 - 2019年美国国家健康与营养检查调查(NHANES)的证据
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Comparative analysis of the postadmission and antemortem oropharyngeal and rectal swab microbiota of ICU patients.对比分析 ICU 患者入院后和死亡前口咽及直肠拭子的微生物群落。
Sci Rep. 2024 Nov 8;14(1):27179. doi: 10.1038/s41598-024-78102-1.
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The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy.脓毒症中的肠道微生物群:从失调到个性化治疗。
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