Clinical implementation of routine whole-genome sequencing for hospital infection control of multi-drug resistant pathogens

B. Forde, H. Bergh, Thom Cuddihy, K. Hajkowicz, Trish Hurst, E. Playford, B. Henderson, N. Runnegar, J. Clark, A. Jennison, S. Moss, A. Hume, Hugo Leroux, S. Beatson, D. Paterson, P. Harris
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引用次数: 16

Abstract

Background: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting. Materials/methods: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MSLT) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams. Results: Over four years (April 2017 to July 2021) 2,660 isolates were sequenced. This included MDR gram-negative bacilli (n=293 CPE, n=1309 ESBL), MRSA (n=620) and VRE (n=433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the three target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In one hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy. Conclusions: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.
临床实施常规全基因组测序用于多药耐药病原菌医院感染控制
背景:基于前瞻性全基因组测序(WGS)的监测可能是快速识别医疗保健环境中多重耐药(MDR)细菌传播的最佳方法。材料/方法:我们前瞻性地收集了澳大利亚布里斯班三家大型三级转诊医院(2家成人医院,1家儿科医院)从血液培养、无菌地点或筛选标本中分离到的耐甲氧西林金黄色葡萄球菌(MRSA)、耐万古霉素肠球菌(VRE)、耐碳青霉烯类鲍曼不动杆菌(CRAB)、广谱β -内酰胺酶(esble)和产碳青霉烯酶肠杆菌(CPE)。WGS用于通过定制的基因组分析管道确定硅多位点序列分型(MSLT)和抗性基因谱。通过比较核心基因组单核苷酸多态性(snp)来确定可能的传播事件。相关临床元数据通过定制自动化与基因组分析相结合,整理成医院特定报告,定期分发给感染控制团队。结果:4年间(2017年4月至2021年7月)对2660株菌株进行了测序。其中包括MDR革兰氏阴性杆菌(n=293 CPE, n=1309 ESBL), MRSA (n=620)和VRE (n=433)。共发表临床报告379份。核心基因组SNP数据确定33%的分离株形成76个不同的簇。在76例聚集性病例中,有43例被控制在三家目标医院,表明在临床环境中正在进行传播。其余33个聚集性病例代表可能的医院间传播事件或在社区中流行的菌株。在一家医院,非多重耐药MRSA的传播被证明可以忽略不计,从而改变了感染控制政策。结论:临床实验室对耐多药病原菌实施常规WGS检测是可行的,可实现有针对性的感染防控干预。
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