Post Virginia, Wahl Peter, Richards R Geoff, Moriarty T Fintan
AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
Division for Orthopaedic and Trauma Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland.
J Orthop Res. 2017 Feb;35(2):381-388. doi: 10.1002/jor.23291. Epub 2016 May 29.
This study was carried out to determine the time and concentration profile required to achieve vancomycin-mediated eradication of Staphylococcus aureus biofilm. This information is critical for the identification of performance targets for local antibiotic delivery vehicles that target biofilm infections. S. aureus UAMS-1 biofilms were grown for 7 days on titanium-aluminium-niobium discs in Mueller Hinton broth. After 7 days, the discs were then incubated in Mueller Hinton broth containing vancomycin at concentrations of 100, 200, 500, 1,000, and 2,000 mg/L. Biofilm eradication was assessed under both static and shaking conditions. Samples were retrieved at regular intervals for up to 28 days for quantification of residual biofilm. One additional disc was processed per time point for scanning electron microscopy. Progressive and significant reduction of viable bacteria was observed over time at all concentrations compared to unexposed controls. After 28 days under static conditions, the S. aureus biofilm was completely eradicated at 200 mg/L vancomycin and higher concentrations, but not at 100 mg/L. In contrast, bacterial biofilm could not be eradicated under shaking conditions at any concentration.
The present study shows that it is possible to eradicate mature S. aureus biofilm from metal implants by vancomycin alone although the time concentration profile required cannot be achieved by systemic administration or any of the local delivery vehicles currently available. Identifying targets for antibiotic delivery is the first step in developing fit for purpose local antibiotic delivery vehicles that will successfully and predictably treat established biofilm infection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:381-388, 2017.
本研究旨在确定实现万古霉素介导的金黄色葡萄球菌生物膜根除所需的时间和浓度曲线。该信息对于确定针对生物膜感染的局部抗生素递送载体的性能目标至关重要。金黄色葡萄球菌UAMS-1生物膜在穆勒-欣顿肉汤中于钛铝铌盘上培养7天。7天后,将圆盘在含有浓度为100、200、500、1000和2000mg/L万古霉素的穆勒-欣顿肉汤中孵育。在静态和振荡条件下评估生物膜的根除情况。每隔一定时间取样长达28天,以定量残留生物膜。每个时间点额外处理一个圆盘用于扫描电子显微镜检查。与未暴露的对照相比,在所有浓度下随着时间的推移均观察到活菌数量逐渐且显著减少。在静态条件下28天后,200mg/L及更高浓度的万古霉素可完全根除金黄色葡萄球菌生物膜,但100mg/L时不能。相比之下,在振荡条件下,任何浓度均不能根除细菌生物膜。
本研究表明,仅用万古霉素就有可能从金属植入物中根除成熟的金黄色葡萄球菌生物膜,尽管通过全身给药或目前任何局部递送载体都无法实现所需的时间-浓度曲线。确定抗生素递送的目标是开发适合目的的局部抗生素递送载体的第一步,该载体将成功且可预测地治疗已形成的生物膜感染。©2016骨科学研究协会。由威利期刊公司出版。《矫形外科学研究》35:381 - 388,2017年。