关键词: Candida parapsilosis ERG11 GATK MycoSNP antifungal susceptibility testing fluconazole resistance microsatellite typing outbreak phylogenomic analysis whole genome sequencing

Mesh : Humans Fluconazole / pharmacology Candida parapsilosis Retrospective Studies Microbial Sensitivity Tests Drug Resistance, Fungal / genetics Antifungal Agents / pharmacology therapeutic use Genomics Hospitals Ontario

来  源:   DOI:10.1128/jcm.01161-23   PDF(Pubmed)

Abstract:
Candida parapsilosis is a common cause of non-albicans candidemia. It can be transmitted in healthcare settings resulting in serious healthcare-associated infections and can develop drug resistance to commonly used antifungal agents. Following a significant increase in the percentage of fluconazole (FLU)-nonsusceptible isolates from sterile site specimens of patients in two Ontario acute care hospital networks, we used whole genome sequence (WGS) analysis to retrospectively investigate the genetic relatedness of isolates and to assess potential in-hospital spread. Phylogenomic analysis was conducted on all 19 FLU-resistant and seven susceptible-dose dependent (SDD) isolates from the two hospital networks, as well as 13 FLU susceptible C. parapsilosis isolates from the same facilities and 20 isolates from patients not related to the investigation. Twenty-five of 26 FLU-nonsusceptible isolates (resistant or SDD) and two susceptible isolates from the two hospital networks formed a phylogenomic cluster that was highly similar genetically and distinct from other isolates. The results suggest the presence of a persistent strain of FLU-nonsusceptible C. parapsilosis causing infections over a 5.5-year period. Results from WGS were largely comparable to microsatellite typing. Twenty-seven of 28 cluster isolates had a K143R substitution in lanosterol 14-α-demethylase (ERG11) associated with azole resistance. As the first report of a healthcare-associated outbreak of FLU-nonsusceptible C. parapsilosis in Canada, this study underscores the importance of monitoring local antimicrobial resistance trends and demonstrates the value of WGS analysis to detect and characterize clusters and outbreaks. Timely access to genomic epidemiological information can inform targeted infection control measures.
摘要:
近带念珠菌病是非白色念珠菌病的常见原因。它可以在医疗机构中传播,导致严重的医疗保健相关感染,并可能对常用的抗真菌药物产生耐药性。在两个安大略省急性护理医院网络中,来自患者无菌部位标本的氟康唑(FLU)-非易感分离株的百分比显着增加,我们使用全基因组序列(WGS)分析回顾性调查分离株的遗传相关性,并评估潜在的院内传播.对来自两个医院网络的所有19种FLU抗性和7种易感剂量依赖性(SDD)分离株进行了系统发育分析。以及来自同一设施的13个FLU易感近平滑梭菌分离株和来自与调查无关的患者的20个分离株。来自两个医院网络的26个FLU非易感分离株(抗性或SDD)中的25个和两个易感分离株形成了系统基因组簇,该系统簇在遗传上高度相似,并且与其他分离株不同。结果表明,在5.5年的时间内,存在持续存在的FLU不敏感的近apsilia。来自WGS的结果在很大程度上与微卫星分型相当。28个簇分离株中的27个在与唑类抗性相关的羊毛甾醇14-α-脱甲基酶(ERG11)中具有K143R取代。作为加拿大与医疗保健相关的FLU-非易感梭菌暴发的第一份报告,本研究强调了监测当地抗菌素耐药趋势的重要性,并证明了WGS分析对发现和表征集群和暴发的价值.及时获取基因组流行病学信息可以为有针对性的感染控制措施提供信息。
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