Schwartz Franziska A, Nielsen Luna, Struve Andersen Jessica, Bock Magnus, Christophersen Lars, Sunnerhagen Torgny, Lerche Christian Johann, Bay Lene, Bundgaard Henning, Høiby Niels, Moser Claus
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Department of Technology, Faculty of Health, University College Copenhagen, Copenhagen, Denmark.
APMIS. 2022 Aug;130(8):515-523. doi: 10.1111/apm.13231. Epub 2022 May 27.
Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24 h. The bacteria were organized in biofilm aggregates and displayed increased tolerance toward antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a Staphylococcus aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6 h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6 h, accelerating the screening for optimal treatment strategies for IE.
感染性心内膜炎(IE)是一种严重的心脏内表面感染,由心内膜的微小病变引起。这种损伤引发愈合反应,导致纤维蛋白和免疫细胞聚集。这种无菌的愈合性赘生物在暂时性菌血症期间可被细菌定植,从而引发感染性心内膜炎。我们之前利用全静脉血构建的模拟感染性心内膜炎赘生物(IEV)模型建立了一种新型体外感染性心内膜炎模型,在该模型上24小时后实现了稳定的细菌定植。细菌形成生物膜聚集体,并对抗生素表现出更高的耐受性。在本研究中,我们旨在进一步表征生物膜形成的时间进程以及对抗生素耐受性发展的影响。我们发现,一株金黄色葡萄球菌参考菌株以及三株临床感染性心内膜炎分离株在6小时后在IEV上形成了生物膜。感染后立即开始治疗时,抗生素效果明显高于生物膜成熟后开始治疗的情况。我们可以通过观察IEV上生长的细菌聚集体,在显微镜下追踪生物膜的发展。研究结果表明,在我们的模型中,6小时后即可形成成熟的、具有抗生素耐受性的生物膜,这加快了对感染性心内膜炎最佳治疗策略的筛选。