Department of Pharmacology, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S 1085, 2 avenue du Professeur Léon Bernard, F-35000 Rennes, France.
Univ Rennes, Inserm, BRM (Bacterial Regulatory RNAs and Medicine), UMR_S 1230, 2 avenue du Professeur Léon Bernard, F-35000 Rennes, France.
J Antimicrob Chemother. 2023 Jul 5;78(7):1689-1693. doi: 10.1093/jac/dkad155.
Staphylococcal infective endocarditis (IE) remains a hard-to-treat infection with high mortality. Both the evaluation of new innovative therapies and research on alternative models mimicking human IE are therefore urgently needed to improve the prognosis of patients with diagnosed IE. Dalbavancin is a novel anti-staphylococcal lipoglycopeptide but there are limited data supporting its efficacy on biofilm infections. This antibiotic could be an alternative to current therapies for the medical treatment of IE but it needs to be further evaluated.
Here we developed an original ex vivo model of Staphylococcus aureus IE on human heart valves and assessed biofilm formation on them. After validating the model, the efficacy of two antistaphylococcal antibiotics, vancomycin and dalbavancin, was compared by measuring and visualizing their respective ability to inhibit and eradicate late-formed biofilm.
Determination of the minimum biofilm inhibitory (MbIC) and eradicating (MbEC) concentrations in our ex vivo model identified dalbavancin as a promising drug with much lower MbIC and MBEC than vancomycin (respectively <0.01 versus 28 mg/L and 0.03 versus 32 mg/L).
These data highlight a strong bactericidal effect of dalbavancin, particularly on an infected heart valve compared with vancomycin. Dalbavancin could be a realistic alternative treatment for the management of staphylococcal IE.
金黄色葡萄球菌感染性心内膜炎（IE）仍然是一种难以治疗的感染，死亡率很高。因此，迫切需要评估新的创新疗法，并研究模拟人类 IE 的替代模型，以改善确诊 IE 患者的预后。达巴万星是一种新型抗葡萄球菌糖肽，但关于其在生物膜感染方面疗效的数据有限。这种抗生素可能是治疗 IE 的现有疗法的替代选择，但需要进一步评估。
在这里，我们开发了一种在人心脏瓣膜上的金黄色葡萄球菌 IE 的原始离体模型，并评估了它们的生物膜形成。在验证该模型后，通过测量和可视化两种抗葡萄球菌抗生素万古霉素和达巴万星各自抑制和清除晚期形成的生物膜的能力，比较了它们的疗效。
在我们的离体模型中确定最小生物膜抑制浓度（MbIC）和最小生物膜清除浓度（MbEC），发现达巴万星是一种很有前途的药物，其 MbIC 和 MBEC 均显著低于万古霉素（分别为<0.01 与 28 mg/L 和 0.03 与 32 mg/L）。
这些数据突出了达巴万星的强大杀菌作用，特别是与万古霉素相比，在感染的心脏瓣膜上。达巴万星可能是治疗金黄色葡萄球菌 IE 的一种现实替代治疗方法。
