Smit Pieter W, van Tienen Carla, Landman Fabian, Zagers Sabrina, den Drijver Marije, Burggraaf Arjan, Notermans Daan W, Damen Marjolein, Hendrickx Antoni P A, Jamin Casper
Maasstad Laboratories, Medical Microbiology, Molecular Diagnostics Unit, Maasstad Hospital, Rotterdam, Netherlands.
Center for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Microb Genom. 2025 Jan;11(1). doi: 10.1099/mgen.0.001335.
Genes encoding OXA-48-like carbapenem-hydrolyzing enzymes are often located on plasmids and are abundant among carbapenemase-producing (CPE) worldwide. After a large plasmid-mediated outbreak in 2011, routine screening of patients at risk of CPE carriage on admission and every 7 days during hospitalization was implemented in a large hospital in the Netherlands. The objective of this study was to investigate the dynamics of the hospitals' 2011 outbreak-associated plasmid among CPE collected from 2011 to 2021. A selection of 86 -carrying CPE isolates was made from 374 isolates collected over an 11-year study period. Species included (Eco), (Kpn), (Ecl), (Cfr), (Cko) and (Mmo). Short-read sequencing was combined with long-read sequencing for all isolates to reconstruct -like plasmids and chromosomes of CPE. MASH, MOBsuite, ResFinder, PlasmidFinder and SNP analyses were performed to study diversity. pOXA-48 plasmids were compared to plasmid sequences that were sequenced for the Dutch CPE surveillance in the same time period. In total for the 86 CPE, 2 failed genomic assemblies and 78 -encoding plasmids were reconstructed, and six genes were located chromosomally. The 2011 outbreak-associated plasmid of 63.6 kb with IncL replicon was found in Cfr, Ecl, Eco, Kpn and Mmo and primarily between 2011 and 2014 and indicated as LR025105 as MASH nearest neighbour. From 2014 onwards, 11 other types of -carrying plasmids with different antibiotic-resistant genes and replicons were discovered, representing the earlier defined distinct pOXA-48 plasmid groups found in the Netherlands. Furthermore, on a national level, the LR025105 plasmid was found after 2015 in many different bacterial backgrounds, highlighting the promiscuous nature of this pOXA-48 plasmid. After a large outbreak in a large hospital in the Netherlands, the composition of the plasmid population in this hospital diversified over time and is in line with national surveillance data. Plasmid sequencing provided valuable insight into the transmission dynamics of -encoding plasmids and showed no indication of the persistence of the 2011 plasmid in the hospital environment.
编码OXA - 48样碳青霉烯水解酶的基因通常位于质粒上，在全球产碳青霉烯酶（CPE）的菌株中广泛存在。2011年发生大规模质粒介导的疫情后，荷兰一家大型医院对有CPE携带风险的患者在入院时以及住院期间每7天进行一次常规筛查。本研究的目的是调查2011年医院疫情相关质粒在2011年至2021年收集的CPE中的动态变化。从11年研究期间收集的374株分离株中选取了86株携带CPE的分离株。菌株包括大肠埃希菌（Eco）、肺炎克雷伯菌（Kpn）、阴沟肠杆菌（Ecl）、产气肠杆菌（Cfr）、科氏柠檬酸杆菌（Cko）和摩氏摩根菌（Mmo）。对所有分离株进行短读长测序与长读长测序相结合，以重建CPE的OXA - 48样质粒和染色体。进行MASH、MOBsuite、ResFinder、PlasmidFinder和SNP分析以研究多样性。将pOXA - 48质粒与同期荷兰CPE监测测序的质粒序列进行比较。在86株CPE中，共有2株基因组组装失败，重建了78个编码OXA - 48的质粒，6个OXA - 48基因位于染色体上。在产气肠杆菌、阴沟肠杆菌、大肠埃希菌、肺炎克雷伯菌和摩氏摩根菌中发现了2011年疫情相关的63.6 kb含IncL复制子的质粒，主要在2011年至2014年期间，作为MASH最近邻被标记为LR025105。从2014年起，发现了另外11种携带OXA - 48的质粒类型，它们具有不同的抗生素抗性基因和复制子，代表了荷兰早期定义的不同pOXA - 48质粒组。此外，在国家层面，2015年后在许多不同细菌背景中发现了LR025105质粒，突出了这种pOXA - 48质粒的混杂性质。在荷兰一家大型医院发生大规模疫情后，该医院OXA - 48质粒群体的组成随时间发生了变化，这与国家监测数据一致。质粒测序为编码OXA - 48的质粒的传播动态提供了有价值的见解，并且没有迹象表明20
