马德里（西班牙）一家三级医院产多种碳青霉烯酶肠杆菌科细菌的发生：一个新的流行病学情况。

Occurrence of multi-carbapenemase-producing Enterobacterales in a tertiary hospital in Madrid (Spain): A new epidemiologic scenario.

机构信息

Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.

Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

J Glob Antimicrob Resist. 2024 Sep;38:281-291. doi: 10.1016/j.jgar.2024.06.012. Epub 2024 Jul 10.

DOI:10.1016/j.jgar.2024.06.012

PMID:38996870

Abstract

INTRODUCTION: Multi-carbapenemase-producing Enterobacterales (M-CPE) are increasingly described. We characterized the M-CPE isolates prospectively recovered in our hospital (Madrid, Spain) over two years (2021-2022). METHODS: We collected 796 carbapenem resistant Enterobacterales (CRE) from clinical and surveillance samples. Carbapenemase production was confirmed with phenotypic (immunochromatographic, disk diffusion) and molecular (PCR, WGS) techniques. Antimicrobial susceptibility was evaluated by a standard broth microdilution method. Clinical and demographic data were collected. RESULTS: Overall, 23 M-CPE (10 Klebsiella pneumoniae, 6 Citrobacter freundii complex, 3 Escherichia coli, 2 Klebsiella oxytoca, and 2 Enterobacter hormaechei) isolates were recovered from 17 patients (3% with CPE, 0.26-0.28 cases per 1000 admissions). OXA-48 + KPC-3 (7/23) and KPC-3 + VIM-1 (5/23) were the most frequent carbapenemase combinations. All patients had prior antibiotics exposure, including carbapenems (8/17). High resistance rates to ceftazidime/avibactam (14/23), imipenem/relebactam (16/23) and meropenem/vaborbactam (7/23) were found. Ceftazidime/avibactam + aztreonam combination was synergistic in all metallo-β-lactamase producers. Clonal and non-clonal related isolates were found, particularly in K. pneumoniae (5 ST29, 3 ST147, 3 ST307) and C. freundii (3 ST8, 2 ST125, 1 ST563). NDM-1 + OXA-48 was introduced with the ST147-K. pneumoniae high-risk clone linked to the transfer of a Ukrainian patient. We identified four possible nosocomial clonal transmission events between patients of the same clone with the same combination of carbapenemases (KPC-3 + VIM-1-ST29-K. pneumoniae, NDM-1 + OXA-48-ST147-K. pneumoniae and KPC-2 + VIM-1-ST145-K. oxytoca). Carbapenemase-encoding genes were located on different plasmids, except for VIM-1 + KPC-2-ST145-K. oxytoca. Cross-species transmission and a possible acquisition overtime was found, particularly between K. pneumoniae and E. coli producing OXA-48 + KPC-3. CONCLUSION: M-CPE is an emerging threat in our hospital. Co-production of different carbapenemases, including metallo-β-lactamases, limits therapeutic options and depicts the need to reinforce infection control measures.

摘要

简介：越来越多的多碳青霉烯酶产生肠杆菌科（M-CPE）被描述。我们在两年（2021-2022 年）内前瞻性地收集了我们医院（西班牙马德里）分离的 M-CPE 菌株。

方法：我们从临床和监测样本中收集了 796 株耐碳青霉烯类肠杆菌科（CRE）。通过表型（免疫层析、纸片扩散）和分子（PCR、WGS）技术确认碳青霉烯酶的产生。采用标准肉汤微量稀释法评估抗菌药物敏感性。收集临床和人口统计学数据。

结果：总体而言，从 17 名患者中分离出 23 株 M-CPE（10 株肺炎克雷伯菌、6 株弗氏柠檬酸杆菌复合体、3 株大肠埃希菌、2 株产酸克雷伯菌和 2 株蜂房哈夫尼菌）（3%的患者产 CPE，每 1000 例入院患者中有 0.26-0.28 例）。OXA-48 + KPC-3（7/23）和 KPC-3 + VIM-1（5/23）是最常见的碳青霉烯酶组合。所有患者均有抗生素暴露史，包括碳青霉烯类药物（17/17）。发现对头孢他啶/阿维巴坦（14/23）、亚胺培南/雷巴坦（16/23）和美罗培南/沃巴坦（7/23）的耐药率很高。所有金属β-内酰胺酶产生菌均对头孢他啶/阿维巴坦+氨曲南组合呈协同作用。发现了克隆和非克隆相关的分离株，尤其是在肺炎克雷伯菌（5 株 ST29、3 株 ST147、3 株 ST307）和弗氏柠檬酸杆菌（3 株 ST8、2 株 ST125、1 株 ST563）中。NDM-1 + OXA-48 与与乌克兰患者转移有关的高风险 ST147-K. pneumoniae 克隆一起引入。我们在具有相同碳青霉烯酶组合的同一克隆的患者之间发现了四个可能的医院内克隆传播事件（KPC-3 + VIM-1-ST29-K. pneumoniae、NDM-1 + OXA-48-ST147-K. pneumoniae 和 KPC-2 + VIM-1-ST145-K. oxytoca）。除了 VIM-1 + KPC-2-ST145-K. oxytoca 外，碳青霉烯酶编码基因位于不同的质粒上。发现了种间传播和可能随时间获得，特别是在产 OXA-48 + KPC-3 的肺炎克雷伯菌和大肠埃希菌之间。

结论：M-CPE 是我们医院的一个新出现的威胁。不同碳青霉烯酶，包括金属β-内酰胺酶的共同产生，限制了治疗选择，并说明了加强感染控制措施的必要性。