[使用 COVID-19 患者的抗生素抗性基因靶向组研究人类微生物群落的抗性组]。
[Study of the resistome of human microbial communities using a targeted panel of antibiotic resistance genes in COVID-19 patients].
发表日期：2023 Dec 28
作者：
O O Yanushevich, I V Maev, N I Krikheli, O V Levchenko, J S Galeeva, E V Starikova, D N Andreev, P S Sokolov, A K Fomenko, M K Devkota, N G Andreev, A V Zaborovsky, V V Evdokimov, S V Tsaregorodtsev, E N Ilina, V M Govorun, P A Bely, E A Sabelnikova, A A Solodov, S V Cheremushkin, R I Shaburov, A L Kebina
来源：
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要：
研究人类肠道微生物组中的整体耐药基因（resistome）以及这些基因在COVID-19住院治疗期间的变化。进行了单中心回顾性队列研究。只有通过聚合酶链反应在口/鼻咽拭子样本中检测到实验室确认的 SARS-CoV-2 RNA 的病例才需要进行分析。有肝胆系统病史或当前合并症、任何部位的恶性肿瘤、全身性和自身免疫性疾病以及孕妇的患者被排除在外。从所有研究对象中收集粪便用于随后的宏基因组测序。最终队列根据疾病严重程度分为两组：轻度（第 1 组）和重度（第 2 组）。在第2组中，根据抗菌药物（ABD）的使用，形成了五个亚组：2A组（接受ABD）、2AC组（住院前接受ABD）、2AD组（住院期间接受ABD）、2AE组（接受ABD）住院期间和住院前），2B 组（未接受 ABD）。接受 ABD 治疗的患者组的抗生素耐药性 (ABR) 基因中位数（所有时间点累积）显着较高：81.0（95% CI 73.8- 84.5) 对比 51.0 (95% CI 31.1-68.4)。在接受 ABD 治疗的患者组 (2A) 中，多药耐药基因（外排系统）的平均数量显着高于对照组（2B 组）：47.0 (95% CI 46.0-51.2) vs. 21.5 (95% CI 7.0-43.9）。严重冠状病毒感染患者的 ABR 基因中位数往往较高，但没有统计学意义。住院前和住院期间未接受 ABD 的重症 COVID-19 组患者也比对照组患者有更多的耐药基因。这项研究表明，病情较轻的组中发现的 ABR 基因比对照组少更严重的疾病与更多的 ABR 基因相关，其中最常见的是以下五种：SULI、MSRC、ACRE、EFMA、SAT。
To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy.A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD).The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8-84.5) vs. 51.0 (95% CI 31.1-68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0-51.2) vs. 21.5 (95% CI 7.0-43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group.This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.