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产 OXA-232 碳青霉烯类耐药肺炎克雷伯菌的医院感染克隆传播株的流行病学特征及其与环境定植的关系

Epidemiological Characteristics of OXA-232-Producing Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated during Nosocomial Clonal Spread Associated with Environmental Colonization.

机构信息

Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang Universitygrid.13402.34 School of Medicine, Hangzhou, Zhejiang Province, China.

Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang Province, China.

出版信息

Microbiol Spectr. 2022 Aug 31;10(4):e0257221. doi: 10.1128/spectrum.02572-21. Epub 2022 Jun 22.

DOI:10.1128/spectrum.02572-21
PMID:35730968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9430510/
Abstract

Here, a program was designed to surveil the colonization and associated infection of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) (OXA-232-CRKP) in an intensive care unit (ICU) and to describe the epidemiological characteristics during surveillance. Samples were sourced from patient and environment colonization sites in the ICU from August to December 2019. During the surveillance, 106 OXA-232-CRKP strains were isolated from 8,656 samples of colonization sites, with an average positive rate of 1.22%. The rate from patient colonization sites was 3.59% (60/1,672 samples), over 5 times higher than that of the environment (0.66% [46/6,984 samples]). Rectal swabs and ventilator-related sites had the highest positive rates among patient and environment colonization sites, respectively. Six of the 15 patients who had OXA-232-CRKP at colonization sites suffered from OXA-232-CRKP-related infections. Patients could obtain OXA-232-CRKP from the environment, while long-term patient colonization was mostly accompanied by environmental colonization with subsequent infection. Antimicrobial susceptibility testing presented similar resistance profiles, in which all isolates were resistant to ertapenem but showed different levels of resistance to meropenem and imipenem. Whole-genome sequencing and single-nucleotide polymorphism (SNP) analysis suggested that all OXA-232-CRKP isolates belonged to the sequence type 15 (ST15) clone and were divided into two clades with 0 to 45 SNPs, sharing similar resistance genes, virulence genes, and plasmid types, indicating that the wide dissemination of OXA-232-CRKP between the environment and patients was due to clonal spread. The strains all contained β-lactam resistance genes, including , , and , and 75.21% additionally carried . In brief, wide ST15 clonal spread and long-term colonization of OXA-232-CRKP between patients and the environment were observed, with microevolution and subsequent infection. OXA-232 is a variant of OXA-48 carbapenemase, which has been increasingly reported in nosocomial outbreaks in ICUs. However, the OXA-232-CRKP transmission relationship between the environment and patients in ICUs was still not clear. Our study demonstrated the long-term colonization of OXA-232-CRKP in the ICU environment, declared that the colonization was a potential risk to ICU patients, and revealed the possible threat that this OXA-232-CRKP clone would bring to public health. The wide dissemination of OXA-232-CRKP between the environment and patients was due to ST15 clonal spread, which presented a multidrug-resistant profile and carried disinfectant resistance genes and virulence clusters, posing a challenge to infection control. The study provided a basis for environmental disinfection, including revealing common environmental colonization sites of OXA-232-CRKP and suggesting appropriate usage of disinfectants to prevent the development of disinfectant resistance.

摘要

这里,我们设计了一个方案,旨在监测产 OXA-232 碳青霉烯类耐药肺炎克雷伯菌(OXA-232-CRKP)在重症监护病房(ICU)中的定植和相关感染情况,并描述监测期间的流行病学特征。样本取自 2019 年 8 月至 12 月 ICU 患者定植部位和环境中的样本。在监测期间,从 8656 份定植部位样本中分离出 106 株 OXA-232-CRKP,阳性率平均为 1.22%。患者定植部位的阳性率为 3.59%(60/1672 份样本),是环境中阳性率(0.66%[46/6984 份样本])的 5 倍以上。患者定植部位中,直肠拭子和呼吸机相关部位的阳性率最高;而环境定植部位中,阳性率最高的是直肠拭子。15 名定植部位携带 OXA-232-CRKP 的患者中,有 6 名发生了 OXA-232-CRKP 相关感染。患者可能从环境中获得 OXA-232-CRKP,而长期的患者定植部位定植大多伴有环境定植,随后发生感染。药敏试验结果显示相似的耐药谱,所有分离株均对厄他培南耐药,但对美罗培南和亚胺培南的耐药程度不同。全基因组测序和单核苷酸多态性(SNP)分析提示,所有 OXA-232-CRKP 分离株均属于 ST15 克隆,分为 2 个分支,具有 0 到 45 个 SNP,具有相似的耐药基因、毒力基因和质粒类型,这表明 OXA-232-CRKP 在环境和患者之间的广泛传播是由于克隆传播所致。这些菌株均携带β-内酰胺类耐药基因,包括blaCTX-M-15、blaDHA-1、blaVEB-1 和 blaOXA-143,75.21%的菌株还携带blaTEM-1B。总之,我们观察到 OXA-232-CRKP 在患者和环境之间的 ST15 克隆广泛传播和长期定植,存在微进化和随后的感染。OXA-232 是 OXA-48 碳青霉烯酶的一种变体,在 ICU 医院感染爆发中已越来越多地被报道。然而,ICU 环境和患者之间 OXA-232-CRKP 的传播关系仍不清楚。我们的研究表明,OXA-232-CRKP 在 ICU 环境中定植时间较长,这对 ICU 患者构成了潜在风险,并揭示了该 OXA-232-CRKP 克隆可能对公共卫生带来的威胁。OXA-232-CRKP 在环境和患者之间的广泛传播是由于 ST15 克隆传播所致,其呈现出一种多药耐药表型,并携带消毒剂耐药基因和毒力簇,这对感染控制构成了挑战。本研究为环境消毒提供了依据,包括揭示了 OXA-232-CRKP 的常见定植部位,并建议适当使用消毒剂,以防止消毒剂耐药性的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/dc51be1a249d/spectrum.02572-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/08c57b672c25/spectrum.02572-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/a7785904a969/spectrum.02572-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/dc51be1a249d/spectrum.02572-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/08c57b672c25/spectrum.02572-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/a7785904a969/spectrum.02572-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af40/9430510/dc51be1a249d/spectrum.02572-21-f003.jpg

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