University of Wisconsin-Madison, Biomedical Engineering, USA.
University of Wisconsin-Madison, Mechanical Engineering, USA.
J Mech Behav Biomed Mater. 2018 Nov;87:80-86. doi: 10.1016/j.jmbbm.2018.06.033. Epub 2018 Jun 28.
Infection incidence for total hip and knee arthroplasty (THA and TKA, respectively) is between 0.2% and 5% and results in approximately 100,000 device failures per year in the United States. Treatment requires prolonged systemic antibiotic therapy with additional surgical revisions. As a prophylactic measure against infection, antibiotics can be incorporated into bone cement during THA and TKA to provide drug administration at the implant site. Antibiotics in bone cement are only effective if they can elute out of the cement at a concentration that is active against common organisms. There is evidence that added antibiotics may affect the cement's mechanical properties, especially at higher dosages. The purposes of this investigation were to (i) determine the mechanical properties of a commercially available bone cement with the addition of vancomycin, (ii) determine the release characteristics of vancomycin added to bone cement, and (iii) evaluate eluted vancomycin efficacy at eliminating some of the most common causative orthopedic implant pathogens. Palacos bone cement was impregnated with incrementally larger clinically relevant weight percentages of vancomycin. Vancomycin is a treatment standard for invasive gram-positive infections, and Palacos cement is one of the most commonly used bone cements. After 21 days of curing in PBS, added masses of vancomycin greater than 0.5 g per 40.0 g cement packet decreased the cement's compressive yield strength to below ISO standard. The addition of vancomycin reduced the bone cement's mechanical properties in compression more than in bending. Vancomycin eluted from Palacos with a steady rise in eluted volume up to 8 days, after which non-therapeutic elution concentrations were observed up to a 60-day end point. The eluted concentration from samples with greater than 0.25 g vancomycin per Palacos packet was sufficient to eliminate a 10 colony forming unit per mL (CFU/mL) initial inoculum of S. aureus, including methicillin-resistant S. aureus (MRSA). However, none of the tested dosages were able to fully clear a 10 CFU/mL initial inoculum of a known high biofilm producing strain of S. epidermidis. When used for infection prophylaxis at the time of THA and TKA, the findings of this study do not support the addition of more than 0.5 g vancomycin to a 40 g packet of Palacos cement due to a reduction in compression yield strength below ISO standards. Vancomycin doses up to 0.5 g were shown to elute from the bone cement matrix and are effective at treating bacterial infections of 10 CFU/mL in bacterial strains of S. aureus, but may have limited effect against high-biofilm producing strains including S. epidermidis.
全髋关节和膝关节置换术(分别为 THA 和 TKA)的感染发生率为 0.2%至 5%,每年导致美国约有 10 万件器械失效。治疗需要长期全身使用抗生素,并进行额外的手术修正。作为预防感染的措施,抗生素可以在 THA 和 TKA 时掺入骨水泥中,以便在植入物部位给药。只有当抗生素从水泥中洗脱出来的浓度对常见生物体有效时,骨水泥中的抗生素才有效。有证据表明,添加抗生素可能会影响水泥的机械性能,尤其是在较高剂量下。本研究的目的是:(i)确定添加万古霉素的市售骨水泥的机械性能,(ii)确定添加到骨水泥中的万古霉素的释放特性,以及(iii)评估洗脱的万古霉素在消除一些最常见的骨科植入物病原体方面的功效。Palacos 骨水泥逐渐用临床相关的较大重量百分比的万古霉素浸渍。万古霉素是治疗侵袭性革兰氏阳性感染的标准治疗方法,而 Palacos 水泥是最常用的骨水泥之一。在 PBS 中固化 21 天后,添加的万古霉素量超过每 40.0g 水泥包 0.5g,会降低水泥的抗压屈服强度,使其低于 ISO 标准。添加万古霉素会降低骨水泥在压缩下的机械性能,超过弯曲下的机械性能。万古霉素从 Palacos 洗脱,洗脱体积稳定上升,直到第 8 天,之后观察到非治疗性洗脱浓度,直至 60 天终点。从每个 Palacos 包添加超过 0.25g 万古霉素的样品中洗脱的浓度足以消除初始接种物为每毫升 10 个菌落形成单位(CFU/mL)的金黄色葡萄球菌,包括耐甲氧西林金黄色葡萄球菌(MRSA)。然而,在所测试的剂量中,没有一种能够完全清除初始接种物为 10 CFU/mL 的已知高生物膜产生表皮葡萄球菌的菌株。在进行 THA 和 TKA 时,作为感染预防措施,本研究的结果不支持在 Palacos 水泥 40g 包装中添加超过 0.5g 万古霉素,因为压缩屈服强度低于 ISO 标准。研究表明,高达 0.5g 的万古霉素可以从骨水泥基质中洗脱出来,并能有效治疗金黄色葡萄球菌的细菌感染,初始接种物为 10 CFU/mL,但对包括表皮葡萄球菌在内的高生物膜产生菌株可能效果有限。